Next generation risk assessment for occupational chemical safety - A real world example with sodium-2-hydroxyethane sulfonate.

Next Generation Risk Assessment (NGRA) is an exposure-led approach to safety assessment that uses New Approach Methodologies (NAMs). Application of NGRA has been largely restricted to assessments of consumer use of cosmetics and is not currently implemented in occupational safety assessments, e.g.

[Interactions between radical prostatovesiculectomy and diagnosis of prostate cancer : A medical-historical inventory on the occasion of 20 years of robot-assisted treatment].

The question of what came first-in this case the diagnosis of prostate cancer or its therapy-seems absurd at first glance and is reminiscent of the classic metaphor-like problem that preoccupied the Greek writer Plutarch (45-125). Today it is a matter of course that a reliable diagnosis is made before treating a disease, but this must be viewed as inconsistent in medical history. The beginnings of radical prostatectomy for the treatment of prostate cancer, like the first surgical therapies for kidney and bladder tumors, can be located in the pioneering period of organ surgery in the German Empire (1871-1918).

Update of OECD DART guidelines with endocrine disruptor relevant endpoints: Practical considerations.

In 1998, the OECD initiated a high-priority project aimed at revising existing test guidelines and developing new test guidelines for screening of potential endocrine disruptors. In 2011, OECD 443 was adopted, and in 2015 OECD 421 and OECD 422 were updated with endocrine disruptor relevant endpoints. A feasibility study for the enhancement of OECD 414 with endocrine disruptor relevant endpoints is currently ongoing.

An Examination of Methodological Paradigms for Calculating Upper Airway Critical Pressures during Sleep.

Study Objectives: The goal of this study was to examine different paradigms for determining critical closing pressures (Pcrit). Methods of determining Pcrit were compared, including direct observation of occluded (no flow) breaths versus inferring Pcrit from extrapolated data, and Pcrit generated by aggregating pressure-flow data from multiple runs versus Pcrit averaged across individual pressure-flow runs. The relationship between Pcrit and obstructive sleep apnea (OSA) was examined.

Racial/Ethnic Disparities in Cumulative Environmental Health Impacts in California: Evidence From a Statewide Environmental Justice Screening Tool (CalEnviroScreen 1.1).

Objectives: We used an environmental justice screening tool (CalEnviroScreen 1.1) to compare the distribution of environmental hazards and vulnerable populations across California communities.

Methods: CalEnviroScreen 1.

Risk and timing of biochemical recurrence in pT3aN0/Nx prostate cancer with positive surgical margin - A multicenter study.

Background And Purpose: Positive surgical margins (PSM) after radical prostatectomy have been shown to be associated with impaired outcome. In pT3pN0 patients with PSM either immediate radiotherapy or clinical and biological monitoring followed by salvage radiotherapy is recommended by the latest guidelines of the European Association of Urology.

Materials And Methods: A retrospective, multicenter study of eight urological centers was conducted on 536 prostatectomy patients with pT3aN0/NxR1 tumors and no neoadjuvant/adjuvant therapy.

Biomodulatory Treatment of Patients with Castration-Resistant Prostate Cancer: A Phase II Study of Imatinib with Pioglitazone, Etoricoxib, Dexamethasone and Low-Dose Treosulfan.

Therapeutic options for patients with castration-resistant prostate cancer (CRPC) remain limited. In a multicenter, Phase II study, 65 patients with histologically confirmed CRPC received a biomodulatory regimen during the six-month core study. Treatment comprised daily doses of imatinib mesylate, pioglitazone, etoricoxib, treosulfan and dexamethasone.

Outcome of patients with pathological tumor stage T3 urothelial carcinoma of the bladder following radical cystectomy in a single-center series with 116 patients.

Objective: Outcome prediction of pT3 urothelial carcinoma of the bladder (UCB) after radical cystectomy (RC) remains challenging. The objective of our study was to determine high-risk patients with poor survival outcome in a heterogeneous group substaged pT3 who might profit from early adjuvant chemotherapy.

Materials And Methods: We compiled clinicopathological and immunohistochemical data of E-cadherin (E-cad) expression in 116 patients with pT3 UCB after RC in our single-center series.

The Charlson comorbidity index predicts survival after disease recurrence in patients following radical cystectomy for urothelial carcinoma of the bladder.

Objective: To identify prognostic clinical and histopathological parameters, including comorbidity indices at the time of radical cystectomy (RC), for overall survival (OS) after recurrence following RC for urothelial carcinoma of the bladder (UCB).

Materials And Methods: A retrospective multicenter study was carried out in 555 unselected consecutive patients who underwent RC with pelvic lymph node dissection for UCB from 2000 to 2010. A total of 227 patients with recurrence comprised our study group.

Association of tissue mRNA and serum antigen levels of members of the urokinase-type plasminogen activator system with clinical and prognostic parameters in prostate cancer.

The objective was to determine the mRNA expression and protein levels of uPA system components in tissue specimens and serum samples, respectively, from prostate cancer (PCa) patients and to assess their association with clinicopathological parameters and overall survival (OS). The mRNA expression levels of uPA, its receptor (uPAR), and its inhibitor type 1 (PAI-1) were analyzed in corresponding malignant and adjacent nonmalignant tissue specimens from 132 PCa patients by quantitative PCR. Preoperative serum samples from 81 PCa patients were analyzed for antigen levels of uPA system members by ELISA.

Correlation of pretreatment clinical parameters and PSA nadir after high-intensity focused ultrasound (HIFU) for localised prostate cancer.

Objective: To determine which pretreatment clinical parameters were predictive of a low prostate-specific antigen (PSA) nadir following high-intensity focused ultrasound (HIFU) treatment.

Patients And Methods: Retrospective study of patients with clinically localised prostate cancer undergoing HIFU at a single centre between December 1997 and September 2009. Whole-gland treatment was applied.

Activated peritoneal cavity B-1a cells possess regulatory B cell properties.

Previous studies have suggested that murine peritoneal cavity-derived B-1a cells possess similarities with described regulatory B cell subsets. The aim of the current study was to examine the potential immunoregulatory function of peritoneal cavity-derived B(-1a) cells. In vitro activation of peritoneal cavity-derived B- and B-1a cells shows that activation of these B cells with anti-CD40 and LPS induces these cells to secrete more IL-10, IL-6 and IgM as compared to splenic B cells.

Mdm2 SNP309 G-variant is associated with invasive growth of human urinary bladder cancer.

Objective: Human mouse double minute 2 (Mdm2) is essential in degrading p53 by acting as an ubiquitin ligase and therefore plays a vital role in cell cycle and survival. The G-variant of the Mdm2 SNP309, which is located within the promoter of the Mdm2 gene, increases expression of Mdm2 and thereby inhibits the p53 pathway. Several studies have investigated the influence of this SNP on disease risk and onset of various malignancies.

Role of two single nucleotide polymorphisms in secreted frizzled related protein 1 and bladder cancer risk.

In this study, we determined the genotype distribution of two single nucleotide polymorphisms (SNPs) in secreted frizzled related protein 1 (SFRP1), rs3242 and rs921142, in a Caucasian bladder cancer case-control study. Allelic variants of the SNPs were determined using restriction fragment length polymorphism (RFLP) analysis and partly verified by sequencing analysis. Overall, DNA from 188 consecutive and 215 early-onset bladder cancer patients (≤45 years) as well as from 332 controls was investigated.

Expression of aquaporin water channels in human urothelial carcinoma: correlation of AQP3 expression with tumour grade and stage.

Purpose: To study the expression, localization and potential clinical significance of aquaporin water channels both in well-established urothelial cancer (UC) cell lines and in human bladder carcinoma specimens of different stages and grades and to discuss the clinical relevance of the findings.

Methods: AQP transcript and protein expression by RT4, RT112 and T24 UC cell lines was investigated using reverse transcriptase polymerase chain reaction and immunofluorescence labelling. Immunohistochemistry (IHC) was used to assess AQP protein expression in 94 UC specimens of various grades and stages.

Do young patients with renal cell carcinoma feature a distinct outcome after surgery? A comparative analysis of patient age based on the multinational CORONA database.

Purpose: We analyzed the distinct clinicopathological features and prognosis of patients with renal cell carcinoma age 40 years or less compared to a reference group of patients 60 to 70 years old.

Materials And Methods: Overall 2,572 patients retrieved from a multicenter international database comprised of 6,234 patients with surgically treated renal cell carcinoma were included in this retrospective study. Clinical and histopathological features of 297 patients 40 years old or younger (4.

Hits and misses: screening commercial drivers for obstructive sleep apnea using guidelines recommended by a joint task force.

Objective: To evaluate joint task force criteria-based screening for severe obstructive sleep apnea (s-OSA) in commercial drivers.

Methods: Among a community-based cohort of licensed commercial vehicle drivers, we assessed utility of the joint task force criteria. We conducted full, 14-channel overnight polysomnography in all drivers, defining s-OSA as an apnea-hypopnea index of 30 or more per hour.

Introduction and first clinical application of a simplified immunohistochemical validation system confirms prognostic impact of KI-67 and CK20 for stage T1 urothelial bladder carcinoma: single-center analysis of eight biomarkers in a series of three hundred six patients.

Background: Biomarkers could help to estimate the prognosis of solid tumors. One of the reasons that many immunohistochemical (IHC) markers are not used routinely is the high interobserver variability and various cutoff values. In the present study, we used a simplified IHC method with a group of 8 biomarkers in stage pT1 urothelial bladder carcinoma (UBC).

Oncological outcome of primary versus secondary muscle-invasive bladder cancer is comparable after radical cystectomy.

Background: High-risk non-muscle-invasive bladder cancer (NMIBC) progressing to muscle-invasive bladder cancer (MIBC) is associated with adverse tumour biology. It is unclear, however, whether outcome of NMIBC progressing to MIBC is adverse compared to primary MIBC and whether NMIBC of higher risk of progression to MIBC is adverse compared to NMIBC of lower risk.

Objective: Our objective was to assess cancer-specific survival (CSS) following radical cystectomy (RC) for primary MIBC and for NMIBC progressing to MIBC in dependence of EORTC risk score.

Clinical and pathological nodal staging score for urothelial carcinoma of the bladder: an external validation.

Purpose: Radical cystectomy (RC) and pelvic lymph node dissection (LND) are standard treatments for muscle-invasive urothelial carcinoma of the bladder. Lymph node staging is a prerequisite for clinical decision-making regarding adjuvant chemotherapy and follow-up regimens. Recently, the clinical and pathological nodal staging scores (cNSS and pNSS) were developed.

Peritoneal cavity B-1a cells promote peripheral CD4+ T-cell activation.

Innate-like murine B-1a cells are well known for their ability to secrete natural IgM. Their non-Ab mediated functions, including Ag presentation to CD4(+) T cells, are less well explored. Using combined adoptive transfer experiments with peptide-pulsed peritoneal cavity (PerC)-derived B-1a cells and CFSE-labeled T cells, we show that B-1a cells present Ag to CD4(+) T cells from the periphery in vivo.

Computerized quantification and planimetry of prostatic capsular nerves in relation to adjacent prostate cancer foci.

Background: Perineural invasion is discussed as a significant route of extraprostatic extension in prostate cancer (PCa). Recent in vitro studies suggested a complex mechanism of neuroepithelial interaction.

Objective: The present study was intended to investigate whether the concept of neuroepithelial interaction can be supported by a quantitative analysis and planimetry of capsular nerves in relation to adjacent PCa foci.

Lack of evidence for frequent MED12 p.L1224F mutation in prostate tumours from Caucasian patients.

Recently mutations in the MED12 gene have been reported in 5.4% of prostate tumours from Caucasian patients analysed by exome sequencing (Barbieri CE, Baca SC, Lawrence MS, et al. Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer.