Aristolochic acid, a potent human carcinogen produced by Aristolochia plants, is associated with urothelial carcinoma of the upper urinary tract (UUC). Following metabolic activation, aristolochic acid reacts with DNA to form aristolactam (AL)-DNA adducts. These lesions concentrate in the renal cortex, where they serve as a sensitive and specific biomarker of exposure, and are found also in the urothelium, where they give rise to a unique mutational signature in the TP53 tumor-suppressor gene. Using AL-DNA adducts and TP53 mutation spectra as biomarkers, we conducted a molecular epidemiologic study of UUC in Taiwan, where the incidence of UUC is the highest reported anywhere in the world and where Aristolochia herbal remedies have been used extensively for many years. Our study involves 151 UUC patients, with 25 patients with renal cell carcinomas serving as a control group. The TP53 mutational signature in patients with UUC, dominated by otherwise rare A:T to T:A transversions, is identical to that observed in UUC associated with Balkan endemic nephropathy, an environmental disease. Prominent TP53 mutational hotspots include the adenine bases of 5′ AG (acceptor) splice sites located almost exclusively on the nontranscribed strand. A:T to T:A mutations also were detected at activating positions in the FGFR3 and HRAS oncogenes. AL-DNA adducts were present in the renal cortex of 83% of patients with A:T to T:A mutations in TP53, FGFR3, or HRAS. We conclude that exposure to aristolochic acid contributes significantly to the incidence of UUC in Taiwan, a finding with significant implications for global public health.upper urinary tract carcinoma | traditional Chinese medicine | transitional cell carcinoma | DNA damage | herbal medicine

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expression in the human fetal prostate is contemporaneous with the fetal testosterone surge and with ductal budding of the prostatic urothelium. expression is also present in the female urogenital sinus but in the absence of testosterone it is not associated with ductal budding.

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Bladder cancer is a common disease representing the fifth most diagnosed solid tumor in the United States. Despite this, advances in our understanding of the molecular etiology and treatment of bladder cancer have been relatively lacking. This is especially apparent when recent advances in other cancers, such as breast and prostate, are taken into consideration. The field of bladder cancer research is ready and poised for a series of paradigm-shifting discoveries that will greatly impact the way this disease is clinically managed. Future preclinical discoveries with translational potential will require investigators to take full advantage of recent advances in molecular and animal modeling methodologies. We present an overview of current preclinical models and their potential roles in advancing our understanding of this deadly disease and for advancing care.

Background: This study aimed to compare the efficacy and safety of oral tranexamic acid (TXA) with intravenous (IV) TXA in reducing perioperative blood loss in total-knee arthroplasty (TKA) and total-hip arthroplasty (THA). Methods: PubMed, Web of Science, Embase, and Cochrane Library were fully searched for relevant studies. Studies comparing the efficacy and safety of oral TXA with IV TXA in TKA and THA were included in this research. Odds ratio (OR) or risk difference (RD) was applied to compare dichotomous variables, while mean difference (MD) was used to compare continues variables. Results: A total of 7 studies (5 randomized controlled trials and 2 retrospective studies) were included into this study. As for patients undergoing TKA or THA, there were no obvious differences between oral TXA group and IV TXA group in hemoglobin (Hb) drop (MD = 0.06, 95% confidence interval [CI] = −0.01 to 0.13, P = .09), transfusion rate (OR = 0.78, 95% CI = 0.54–1.13, P = .19), total blood loss (MD = 16.31, 95% CI = −69.85 to 102.46, P = .71), total Hb loss (MD = 5.18, 95% CI = −12.65 to 23.02, P = .57), length of hospital stay (MD = -0.06, 95% CI = −0.30 to 0.18, P = .63), drain out (MD = 21.04, 95% CI = −15.81 to 57.88, P = .26), incidence of deep vein deep vein thrombosis (RD = 0.00, 95% CI = −0.01 to 0.01, P = .82) or pulmonary embolism (RD = 0.00, 95% CI = −0.01 to 0.01, P = .91). The sample size of this study was small and several included studies were with relatively low quality. Conclusion: Oral TXA is equivalent to IV TXA in reducing perioperative blood loss and should be recommended in TKA and THA. More high-quality studies are needed to elucidate this issue.

In this paper we present a novel hardware architecture for real-time image compression implementing a fast, searchless iterated function system (SIFS) fractal coding method. In the proposed method and corresponding hardware architecture, domain blocks are fixed to a spatially neighboring area of range blocks in a manner similar to that given by Furao and Hasegawa. A quadtree structure, covering from 32 · 32 blocks down to 2 · 2 blocks, and even to single pixels, is used for partitioning. Coding of 2 · 2 blocks and single pixels is unique among current fractal coders. The hardware architecture contains units for domain construction, zig-zag transforms, range and domain mean computation, and a parallel domain-range match capable of concurrently generating a fractal code for all quadtree levels. With this efficient, parallel hardware architecture, the fractal encoding speed is improved dramatically. Additionally, attained compression performance remains comparable to traditional searchbased and other searchless methods. Experimental results, with the proposed hardware architecture implemented on an Altera APEX20K FPGA, show that the fractal encoder can encode a 512 · 512 · 8 image in approximately 8.36 ms operating at 32.05 MHz. Therefore, this architecture is seen as a feasible solution to real-time fractal image compression.