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OBJECTIVE: We aimed to verify whether fetal microchimerism, because of persisting fetal hematopoietic CD34(+) cells from previous pregnancies, could interfere with the development of genetic tests based on using these cells, isolated from maternal blood for the diagnosis of fetal aneuploidies. STUDY DESIGN: CD34(+) cells, isolated from blood of parous women with at least 1 son and nulliparous women, were analyzed by using qualitative polymerase chain reaction (PCR), quantitative PCR, and fluorescence in situ hybridization (FISH) to establish whether these molecular techniques are concurrently capable of detecting circulating male DNA. RESULTS: By qualitative PCR, male DNA was found both in parous and nulliparous women, whereas by quantitative PCR and FISH analyses, no male DNA or male nuclei were revealed except in 1 cultured CD34(+) sample from a nulliparous woman. CONCLUSION: Fetal hematopoietic CD34(+) cells can be used in the noninvasive prenatal testing of fetal aneuploidies because the presence of fetal microchimerism does not affect fetal diagnosis in current pregnancies. [ABSTRACT FROM AUTHOR]

Purpose: Currently, bladder cancer (BC) surveillance consists of periodic white light cystoscopy and urinary cytology (UC). However, both diagnostic tools have limitations. Therefore, to improve the management of recurrent BC, novel, innovative diagnostic tests are needed. The primary aim of this study was to determine the diagnostic performance of Bladder EpiCheck (BE) and photodynamic diagnosis (PDD) guided cystoscopy in the surveillance of high-risk BC. A secondary aim was to compare Bladder EpiCheck (BE) and PDD-guided cystoscopy findings with whose of UC to design a diagnostic algorithm that facilitates clinical decision making. PATIENTS AND METHODS: This was a prospective, blinded, single-arm, single-visit cohort study. All patients were under surveillance for high-risk non-muscle-invasive bladder cancer, and underwent cystoscopy with PDD and a BE test. Those who received a histological diagnosis were used as a reference population. Receiver operating characteristic curve analysis was performed to evaluate the diagnostic performance of BE, PDD-guided cystoscopy, and UC for identifying biopsy-confirmed BC lesions. The diagnostic power of the test was assessed by determining the area under the curve (AUC)., Results: Forty patients were enrolled. For BE, the AUC was 0.95, and BC recurrence was detected at a sensitivity of 100% and specificity of 90.9%. For PDD, the AUC was 0.51, with a sensitivity and specificity of 61% and 41%, respectively. BE was combined with UC to create a decision-making algorithm capable of reducing the number of follow-up cystoscopies needed., Conclusion: BE is a very accurate diagnostic tool that has the potential to be useful in the surveillance of high-risk BC patients. Especially when combined with UC, it may be used to reduce the number of cystoscopies needed throughout follow-up. Conversely, the use of PDD as a diagnostic tool in such patients should be reconsidered. However, due to the small sample size of this study, a larger prospective clinical trial should be performed to confirm findings., Competing Interests: Conflict of interest The authors declare they have no conflict of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Clear cell renal cell carcinoma (ccRCC) is the most common type of renal cell carcinoma, and the absence of symptoms in the early stages makes metastasis more likely and reduces survival. To aid in the early diagnosis of ccRCC, we recently developed a method based on urinary miR-122-5p, miR-1271-5p, and miR-15b-5p levels and three controls. The study here presented aimed to validate the previously published method through its application on an independent cohort. The expression of miRNAs in urine specimens from 28 ccRCC patients and 28 healthy subjects (HSs) of the same sex and age was evaluated by RT-qPCR. Statistical analyses were performed, including the preparation of receiver operating characteristic (ROC) curves. The mean ccRCC diameter in ccRCC patients was 4.2 ± 2.4 mm. Urinary miRNA levels were higher in patients than in HSs. The data were processed using the previously developed algorithm (7p-urinary score), and the area under the curve (AUC) of the algorithm's ROC curve was 0.81 ( p -value = 0.0003), with a sensitivity of 96% and specificity of 65%. Therefore, the 7p-urinary score is a potential tool for the early diagnosis of ccRCC.

The lack of symptoms at the early stages of clear cell renal cell carcinoma (ccRCC) allows the tumour to metastasize, leading to a dramatic reduction in patient survival. Therefore, we studied and set up a method based on urinary microRNAs (miRNAs) for the diagnosis of ccRCC. First, miRNA expression in ccRCC specimens and kidney tissues from healthy subjects (HSs) was investigated through analysis of data banks and validated by comparing expression of miRNAs in ccRCC and adjacent non-cancerous kidney tissue specimens by RT-qPCR. Subsequently, we developed an algorithm to establish which miRNAs are more likely to be found in the urine of ccRCC patients that indicated miR-122, miR-1271, and miR-15b as potential interesting markers. The evaluation of their levels and three internal controls in the urine of 13 patients and 14 HSs resulted in the development of a score (7p-urinary score) to evaluate the presence of ccRCC in patients. The resulting area under the Receiver Operating Characteristic (ROC) curve, sensitivity, and specificity were equal to 0.96, 100% (95% CI 75-100%), and 86% (95% CI 57-98%), respectively. In conclusion, our study provides a proof of concept that combining the expression values of some urinary miRNAs might be useful in the diagnosis of ccRCC.

Many different genetic alterations, as well as complex epigenetic interactions, are the basis of the genesis and progression of prostate cancer (CaP). This is the reason why until now the molecular pathways related to development of this cancer were only partly known, and even less those that determine aggressive or indolent tumour behaviour. MicroRNAs (miRNAs) represent a class of about 22 nucleotides long, small non-coding RNAs, which are involved in gene expression regulation at the post-transcriptional level. MiRNAs play a crucial role in regulating several biological functions and preserving homeostasis, as they carry out a wide modulatory activity on various molecular signalling pathways. MiRNA genes are placed in cancer-related genomic regions or in fragile sites, and they have been proven to be involved in the main steps of carcinogenesis as oncogenes or oncosuppressors in many types of cancer, including CaP. We performed a narrative review to describe the relationship between miRNAs and the crucial steps of development and progression of CaP. The aims of this study were to improve the knowledge regarding the mechanisms underlying miRNA expression and their target genes, and to contribute to understanding the relationship between miRNA expression profiles and CaP., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Tissue engineering represents a potential and valuable approach for the treatment of urologic pathologies. Bioresorbable polymeric scaffolds can be regarded as effective platforms to surgically treat bladder diseases and subsequently guide the formation of novel tissue after implantation. To this aim, the evaluation of electrospun scaffolds made up of poly(ε-caprolactone) blended with poly(3-hydroxybutyrate-co-3-hydroxyvalerate) is presented here. Firstly, the microstructure and the viscoelastic/mechanical properties of the electrospun fabrics were investigated. Then, the in vivo response was assessed by performing a urinary bladder augmentation using female Wistar rats as an animal model. 15 days after the surgical procedure, the scaffolds were covered by regenerative urothelium up to 50%, which increased to 50-100% after 30 days. These encouraging results, collected in the 90-day follow-up, clearly showed the potential applications of tissue engineering in the urologic field. A longer in vivo evaluation is currently underway.

Background: The association of factor V and factor II mutations with preeclampsia and hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome, and a possible role of the two thrombophilic mutations in the pathogenesis of the diseases have been previously investigated. The results, however, are still inconclusive and contradictory., Methods: A case-control study was performed over an interval of 24 months, on 111 subjects with preeclampsia and 111 normal pregnant women matched for age and parity, without previous thromboembolic disorders. The subjects were tested for the mutation A1691G in the factor V gene (R506Q or Leiden mutation) and the mutation A20210G in the factor II (prothrombin) gene. The Student's t-test and the chi2-test were applied when appropriate, and odds ratios and 95% confidence intervals were calculated., Results: Fourteen patients with preeclampsia (12.6%) had at least one of the two mutations, as compared with six controls (5.4%). Factor V Leiden was found in eight patients with preeclampsia (7.2%) and in five controls (4.5%). Factor II G20210A was detected in eight preeclamptic women (7.2%) and in one normal pregnant woman (0.9%)(p = 0.041). In the subgroup of 32 preeclamptic subjects with HELLP syndrome, factor V Leiden was found in three patients (9.3%) and factor II G20210A in two (6.2%)., Conclusions: The prevalence of factor V and factor II mutations is increased in patients with preeclampsia; the thrombophilic mutations may interact with other pathogenic factors to determine the clinical features of the disease and of its complications.

Background: The possibility that changes in activated protein C anticoagulant activity may contribute to the hemostatic changes associated with pregnancy has been previously investigated, but the results of the studies are still controversial., Methods: Nine hundred and sixty-one healthy nonpregnant and 711 normal pregnant women who were noncarriers of factor V Leiden at different weeks' gestation were included in a cross-sectional trial. Moreover, the APC ratio was repeatedly measured in 45 women throughout pregnancy. The activated protein C ratio was tested using the modified activated partial thromboplastin time-based assay., Results: A significantly lower APC ratio was observed at 20-28 and 32-38 (p = 0.0001) weeks' gestation compared with nonpregnant values. The decrease in the APC ratio throughout pregnancy showed a significant trend (p = 0.014). In none of the subjects did the APC ratio reach the cut-off values for APC resistance., Conclusions: Our data confirm a reduction in the APC ratio throughout pregnancy. In our series, an APC ratio of less than 2.0 according to the cut-off point of our laboratory).

Objective: To investigate whether a chronobiological analysis applied to automated 24-hour blood pressure monitoring in early pregnancy provides objective parameters enabling detection of single patients at risk of pregnancy-induced hypertension or preeclampsia., Methods: 24-hour automatic blood pressure monitoring was performed at 8-16 and 20-25 gestational weeks in 104 women at risk of pregnancy-induced hypertension or preeclampsia. The subjects were hospitalized to be synchronized to rest-activity and meal-timing schedules. All women were followed longitudinally until post-partum. Chronobiological analysis of blood pressure values was performed; sensitivity, specificity and predictive values of MESOR and hyperbaric index were also calculated. Incidence of pregnancy-induced hypertension or preeclampsia, gestational week at delivery and birthweight were recorded., Results: Nine thousand nine hundred and eighty-four blood pressure measurements were analyzed. In patients who later developed overt hypertension, systolic and diastolic blood pressure MESOR, hyperbaric index and percent time elevation were already significantly higher in early pregnancy than in those who remained normotensive. The best sensitivity and specificity was obtained between 20-25 weeks of gestation with systolic single cosinor MESOR and Hyperbaric Index using as cut-off 103 mmHg (sensitivity: 88%; specificity: 75%) and 10 mmHg/24 hour (sensitivity: 70%; specificity: 92%), respectively., Conclusions: The chronobiological analysis applied to 24-hour blood pressure monitoring during pregnancy allows definition of objective cut-off values which can be particularly useful in the routine clinical practice when the risk of developing pregnancy-induced hypertension or preeclampsia must be calculated in the individual subject.

Objective: To investigate the effect of 7 to 14 days of therapy with nifedipine (sustained-release preparation) on the 24-hour blood pressure patterns of pregnant women with pre-eclampsia or chronic hypertension, and to test the utility of blood pressure monitoring in modulating the timing and dosage of the drug., Design: 24-hour automatic blood pressure monitoring of pregnant women with pre-eclampsia or chronic hypertension before and after nifedipine treatment., Setting: Centre for Prevention, Diagnosis and Treatment of Hypertension in Pregnancy, University of Turin, Italy., Population: Sixteen pregnant women with pre-eclampsia and 17 with chronic hypertension., Methods: 24-hour blood pressure monitoring was performed before the beginning of the therapy and after 7 to 14 days of treatment with sustained-release nifedipine., Main Outcome Measures: Chronobiological analysis of systolic and diastolic blood pressure values was performed; MESOR, amplitude, acrophase, hyperbaric index, percent time elevation and significance of rhythm were calculated before and after treatment., Results: 6336 blood pressure measurements were analysed. Systolic and diastolic MESOR values were significantly decreased after nifedipine treatment both in pre-eclampsia and in chronic hypertension. However, the antihypertensive effect of nifedipine in pre-eclampsia was especially pronounced during evening and night, while in chronic hypertension it was more constant during the 24-hour period. 24-hour blood pressure monitoring allowed adjustment, when necessary, to the timing and dosage of nifedipine in accordance with the blood pressure patterns of each patient, using the hyperbaric index and percent time elevation as objective parameters for the evaluation of treatment efficacy., Conclusions: 24-hour blood pressure monitoring is a good method to optimise treatment, and confirms that nifedipine is useful for the control of maternal blood pressure in pregnancy.