Genetic imputation of kidney transcriptome, proteome and multi-omics illuminates new blood pressure and hypertension targets.

Genetic mechanisms of blood pressure (BP) regulation remain poorly defined. Using kidney-specific epigenomic annotations and 3D genome information we generated and validated gene expression prediction models for the purpose of transcriptome-wide association studies in 700 human kidneys. We identified 889 kidney genes associated with BP of which 399 were prioritised as contributors to BP regulation. Imputation of kidney proteome and microRNAome uncovered 97 renal proteins and 11 miRNAs associated with BP. Integration with plasma proteomics and metabolomics illuminated circulating levels of myo-inositol, 4-guanidinobutanoate and angiotensinogen as downstream effectors of several kidney BP genes (SLC5A11, AGMAT, AGT, respectively). We showed that genetically determined reduction in renal expression may mimic the effects of rare loss-of-function variants on kidney mRNA/protein and lead to an increase in BP (e.g., ENPEP). We demonstrated a strong correlation (r = 0.81) in expression of protein-coding genes between cells harvested from urine and the kidney highlighting a diagnostic potential of urinary cell transcriptomics. We uncovered adenylyl cyclase activators as a repurposing opportunity for hypertension and illustrated examples of BP-elevating effects of anticancer drugs (e.g. tubulin polymerisation inhibitors). Collectively, our studies provide new biological insights into genetic regulation of BP with potential to drive clinical translation in hypertension.

The Severity of Pain in Prostate Biopsy Depends on the Biopsy Sector.

BACKGROUND: The pain experienced by a patient during a prostate fusion biopsy is cumulative and can also be modulated by many factors. The aim of the study was to assess the association between the degree of pain intensity during prostate biopsy and the region of the biopted organ. MATERIALS AND METHODS: The study included a group of 143 patients who underwent prostate fusion biopsy under local analgesia followed by blockage of the periprostatic nerve. After a biopsy, the patients completed the original questionnaire about the pain experienced during the procedure. RESULTS: There was a statistically significant difference in pain score between cores taken in the apex (median 5 (IQR 2-5)), medium level (median 1 (IQR 1-2)), and prostate base (median 1 (IQR 1-3)) (p < 0.001). The malignancy scale ISUP ≥ 2 (p = 0.038) and lower PSA value (r = -0.17; p = 0.046) are associated with higher pain during procedure. Biopsy time was correlated with discomfort (r = 0.19; p = 0.04). Age (p = 0.65), lesion size (p = 0.29), PI-RADS score (p = 0.86), prostate volume (p = 0.22), and the number of cores (p = 0.56) did not correspond to the pain scale. CONCLUSIONS: The apex is the most sensitive sector of the prostate. ISUP ≥ 2 and patients with low PSA levels more often indicated higher values on the pain rating scale.

The influence of the operator's experience on the outcomes of fusion prostate biopsy.

Introduction: Magnetic resonance imgaing (MRI) targeted biopsy is the gold standard for prostate cancer (PCa) diagnosis. In this study, we examined the association between the operator's experience and the improvement in the precision of the MRI prostate biopsy procedure and the detection of PCa. Material and methods: We included consecutive patients who underwent prostate fusion biopsy. Data on biopsy duration, prostate-specific antigen (PSA) value, lesion size, number of samples taken, number of cores involved, and International Society of Urological Pathology (ISUP) grade were subjected to statistical analysis, with the study group divided into three consecutive time periods (tertiles). Results: There were statistically significant differences in biopsy duration between tertiles (p <0.001). The greatest difference in the involved/taken cores ratio occurred between the first and third tertile (p = 0.002). The difference between the first and second tertile was insignificant (p = 0.4), while the difference between the second and third tertile was statistically significant (p = 0.004). The differences between tertiles in Prostate Imaging and Reporting Data System v2.1 were also significant (p = 0.003). The PSA value (p = 0.036) was statistically significant, unlike prostate volume (p = 0.16), digital rectal examination (DRE) (p = 0.7), and ISUP grade (p = 0.7). There was no statistical difference between tested tertiles in the number of detected PCa ISUP ≥2 (Z = 0.191; p = 0.8). Conclusions: The abilities and precision of the operator increase with the increase in the number of procedures performed. The biopsy duration is shortened, and the detection of PCa during the procedure seems to improve with the operator's experience.

Awareness of testicular cancer among adult Polish men and their tendency for prophylactic self-examination: conclusions from Movember 2020 event.

BACKGROUND: Testicular cancer (TC), due to its non-specific symptoms and occurrence in young men, is particularly dangerous. A critical point for early diagnosis is awareness of the disease and the willingness to perform a testicular self-examination (TSE). The main aim of the study was to assess the knowledge of 771 adult men about testicular cancer. Additionally, the sources of information on TC and TSE were analyzed and the influence of demographic factors on the willingness to join preventative programs was examined. MATERIALS AND METHODS: The study was carried out during the Movember2020 campaign, where a testicular ultrasound was performed on participants. They were asked to complete a questionnaire with 26 questions to assess their knowledge. RESULTS: The results obtained in the study indicate a low level of knowledge (average 3.5 points out of 18) about TC. Living in a large city (OR = 1.467; p = 0.03), as well as an earlier conversation about TC (OR = 1.639; p = 0.002), increased the awareness about the disease. Additionally it showed that many participants do not perform TSE at all (52.4%) and that only few perform TSE frequently (18.4%). Relationship status (OR = 2.832; p < 0.001) and previous conversations about TC (OR = 1.546; p = 0.02) was reported to be the main contributing factors in males deciding to have TSE. CONCLUSIONS: Our research indicates large educational neglect in terms of knowledge about TC and reluctance in performing TSE. It is worth carrying out preventative actions periodically on an increasing scale, not only for the screening of testicular cancer, but also to expand knowledge on this subject.

Changing patterns of urologic emergency visits and admissions during the COVID-19 pandemic: a retrospective, multicenter, nationwide study.

INTRODUCTION: We aimed to examine the change in the number and severity of visits to the emergency departments (EDs) and subsequent admissions for urgent urologic conditions in the early stage of the coronavirus disease 2019 (COVID-19) pandemic in Poland. MATERIAL AND METHODS: We evaluated data from 13 urologic centers in Poland and compared the number of visits to the EDs and subsequent admissions before and after the advent of COVID-19 in 2020, and before and after the escalating national restrictions. Furthermore, data on types of urologic complaints, crucial laboratory parameters, and post-admission procedures were analyzed. RESULTS: In total 1,696 and 2,187 urologic visits (22.45% decrease) and 387 and 439 urologic urgent admissions (11.85% decrease) were reported in given periods in 2020 and 2019, respectively. The year-over-year difference in daily mean visits was clear (36.1 vs. 46.5; p < 0.001). Declines were seen in all complaints but device malfunction. In 2020 daily mean visits and admissions decreased from 40.9 and 9.6 before lockdowns to 30.9 (p < 0.001) and 6.9 (p = 0.001) after severe restrictions, respectively. There was a trend towards more negative laboratory parameter profiles in 2020, with patients who visited the EDs after severe restrictions having twice as high median levels of C-reactive protein (15.39 vs. 7.84, p = 0.03). CONCLUSIONS: The observed declines in ED visits and admissions were apparent with the significant effect of national lockdowns. Our results indicate that some of the patients requiring urgent medical help did not appear at the ED or came later than they would have done before the pandemic, presenting with more severe complaints.

Acquired cystic disease-associated renal cell carcinoma: A clinicopathologic study of eight tumors with clinical follow-up.

Acquired cystic disease-associated renal cell carcinoma (ACD-RCC) is the major RCC subtype in patients with end-stage renal disease, specifically those with ACD on dialysis. Three patients with a total of eight tumors have been selected. The aim of this study was to analyze clinicopathologic, immunohistochemical, and prognostic features of eight ACD-RCCs. Three patients with end-stage renal disease (ESRD) were in the age range of 34-45 years and being treated with hemodialysis. All eight tumors were resected by radical nephrectomy. Two patients had a single ACD-RCC, while one patient had bilateral and multifocal ACD-RCCs. Microscopically, combinations of architectural patterns were identified in all tumors. Intracytoplasmic and intraluminal vacuoles, eosinophilic granular cytoplasm, and prominent nucleoli were universal characteristics of these tumors. Atypical cysts were present in three out of four resected kidneys. Immunohistochemistry (IHC) staining revealed all tumors were strongly and diffusely positive for pan-cytokeratin and α-methylacyl-CoA racemase and variably positive for CK7, CD10, PAX8, EMA, vimentin, cytokeratin, high molecular weight cytokeratin (CK HMW). All cases were negative for Napsin A, CK20, CD117, and CD57. After an average follow-up of 27.5 months (range 3-54 months), all our patients are alive without neoplastic (metastatic or recurrent) disease. Our study supports the finding that ACD-RCC has specific morphologic features and a broad spectrum of architectural patterns. We have found that the immunoprofile of ACD-RCC is distinct from that in other RCCs; however, nonspecific and interpretation of microscopic features in the context of the clinical history can aid the diagnosis. We confirm also the favorable prognosis in ACD-RCC.

How has the COVID-19 pandemic impacted Polish urologists? Results from a national survey.

INTRODUCTION: Poland was initially less affected by the coronavirus disease 2019 (COVID-19) pandemic, however, severe restrictions, and health care restructuration have impacted all areas of medicine, including urology. Therefore, we aimed, via an online survey, to examine the impact of the COVID-19 pandemic on Polish urologists and urology residents. MATERIAL AND METHODS: Between May 15 and June 6, 2020, 229 (28.63% response rate) urologists and urology residents responded to a 28-question online survey. The questionnaire analyzed basic demographic and professional characteristics, and the impact of the COVID-19 pandemic on physicians' everyday work, mental status as well as private life. We further compared the differences between the selected subgroups. RESULTS: Nearly all (96.5%) responders claimed that the pandemic had a moderate to high impact on their everyday clinical practice with the majority of the residents (62.0%) believing that the COVID-19 pandemic will harm their training. Most responders (86.9%) reported over 25% declines in outpatient clinic consultations and 55.9% claimed that their income dropped over 25%. Only 38.9% wanted telemedicine to permanently replace some of the consultations after the pandemic, with residents being significantly more positive about this modality (51.4% vs. 33.1%; p = 0.01). Interestingly, 79.9% noticed the negative psychological effect of the pandemic on their colleagues, and 57.6% felt increased anxiety, sadness, or stress. CONCLUSIONS: This study revealed the complaints and needs of Polish urologists and urology residents after the first wave of the COVID-19 pandemic. There was a significantly negative impact on their work, mental health, and private life.

Differentiation of adult rat mesenchymal stem cells to GABAergic, dopaminergic and cholinergic neurons.

BACKGROUND: Mesenchymal stem cells (MSCs) are able to differentiate into cells from all three germ layers. The aim of the current work was the differentiation rat MSCs into GABAergic, cholinergic and dopaminergic cells. NEW METHOD: In this paper, we present differentiation cocktails with a hippocampal astrocyte conditioned medium and with a glioblastoma conditioned medium. We wanted to maximize the role of endogenous secreted substances by cells from the central nervous system in both combinations. These modifications create a microenvironment of differentiation that is similar to natural conditions. Moreover, the presence of the Cxcr4 receptor on neuron-like cells was investigated first time. RESULTS: Our results show that a differentiation cocktail with a hippocampal astrocyte conditioned medium is the most effective and that 17% Gad67(+) and 7% Acht(+) cells were observed using this protocol. After differentiation using the glioblastoma conditioned medium, 12% Gad67 (+) was observed. The presence of the Cxcr4 migration receptor on Gad67(+) and Th(+) cells were observed, which might suggest the transplantation potential of differentiated cells. COMPARISON WITH EXISTING METHODS: Our results are slightly lower than those of previous studies but when differences in counting cells is taken into account, a comparison of results is really difficult. CONCLUSIONS: These new differentiation cocktails should be further investigated and in the next experiment only a part of MSCs that expressed the Cxcr4 receptor will be differentiated. We suppose that the Cxcr4(+) cells may differentiate more easily and as a result, we may achieve a homogenous population of one phenotype of neurons.