Genomic Scores are Independent of Disease Volume in Men with Favorable Risk Prostate Cancer: Implications for Choosing Men for Active Surveillance.

PURPOSE: We sought to determine whether disease volume at prostate biopsy would correlate with genomic scores among men with favorable risk prostate cancer. MATERIALS AND METHODS: We identified all men with NCCN® (National Comprehensive Cancer Network®) very low and low risk disease who underwent Oncotype DX® prostate testing at our institution from 2013 to 2016. Disease volume was characterized as the percent of positive cores, the number of cores with greater than 50% involvement, the largest involvement of any single core and prostate specific antigen density. Nonparametric testing was performed to compare the median Genomic Prostate Score™ and the likelihood of favorable pathology findings between quartiles of disease volume. RESULTS: We identified 112 (37.8%) and 184 men (62.2%) at NCCN very low and low risk, respectively. Median scores did not differ significantly between disease volume quartiles (all p >0.05). However, the median likelihood of favorable pathology findings statistically differed between volume quartiles (all <0.05). Seven of the 105 men (6.3%) with very low risk disease were reclassified at low risk and 13 of 181 (7.2%) with low risk disease were reclassified at intermediate risk. Genomic disease reclassification did not depend on biopsy tumor volume. CONCLUSIONS: In patients with NCCN very low and low risk prostate cancer genomic scores did not demonstrate meaningfully significant differences by volume based on clinically established cutoff points. Moreover, genomic scores identified and reclassified men with higher risk disease despite generally acceptable surveillance characteristics in this group according to grade and volume. This suggests that in patients at low risk the tumor biological potential measured by genomics rather than by volume should inform decisions on active surveillance candidacy.

Multidose Preservative Free Eyedrops by Selective Removal of Benzalkonium Chloride from Ocular Formulations.

PURPOSE: About 70% of eye drops contain benzalkonium chloride (BAK) to maintain sterility. BAK is an effective preservative but it can cause irritation and toxicity. We propose to mitigate ocular toxicity without compromising sterility by incorporating a filter into an eye drop bottle to selectively remove BAK during the process of drop instillation. METHODS: The filter is a packed bed of particles made from poly(2-hydroxyethyl methacrylate) (pHEMA), which is a common ophthalmic material. We showed that pHEMA particle prepared by using ethoxylated trimethylolpropane triacrylate as crosslinker can be incorporated into a modified eyedrop bottle tip to selectively remove the preservative as the formulation is squeezed out of the bottle. Hydraulic permeability of the plug is measured to determine the resistance to eye drop squeezing, and % removal of BAK and drugs are determined. RESULTS: The modified tip has a hydraulic permeability of about 2 Darcy, which allows eyedrops formulations to flow through without excessive resistance. The tip is designed such that the patients can create an eyedrop of solution of 1-10 cP viscosity in 4 s with a nominal pressure. During this short contact time, the packed particles removed nearly 100% of benzalkonium chloride (BAK) from a 15 mL, 0.012% BAK solution but have only minimal impact on the concentration of contained active components. CONCLUSION: Our novel design can eliminate the preservative induced toxicity from eye drops thereby impacting hundreds of millions of patients with chronic ophthalmic diseases like glaucoma and dry eyes.

Melanoma Antigen Family A (MAGE A) as Promising Biomarkers and Therapeutic Targets in Bladder Cancer.

The Melanoma Antigen Gene (MAGE) is a large family of highly conserved proteins that share a common MAGE homology domain. Interestingly, many MAGE family members exhibit restricted expression in reproductive tissues but are abnormally expressed in various human malignancies, including bladder cancer, which is a common urinary malignancy associated with high morbidity and mortality rates. The recent literature suggests a more prominent role for MAGEA family members in driving bladder tumorigenesis. This review highlights the role of MAGEA proteins, the potential for them to serve as diagnostic or prognostic biomarker(s), and as therapeutic targets for bladder cancer.

Novel Antireflux "RELIEF" Stent to Prevent Vesicoureteral Reflux.

OBJECTIVE: To assess efficacy, comfort, and symptoms of a novel ureteral stent (RELIEF) substituting the distal semirigid coil of a traditional double-J for a floating, monofilament tether allowing coaptation of the ureteral orifice. Ureteral instrumentation notoriously cause discomfort, urgency, frequency, dysuria, and hematuria; prolonged morbidity is likely related to stent-associated vesicoureteral reflux (VUR). We hypothesized this design would eliminate VUR, be safe and provide comfort following intervention. METHODS: Twenty-eight patients within a single institution were enrolled. Passive cystography was performed pre- and post-stent placement assessing VUR. Patients completed Ureteric Stent Symptoms Questionnaires (USSQ) before placement (baseline), postop day 1, and day of removal. RESULTS: Twenty RELIEF stents were placed (11 female and 9 male). 95% demonstrated no VUR following placement. No unexpected adverse complications occurred; 1 patient opted for early stent removal for significant discomfort. Average total USSQ scores demonstrated statistically significant improvement between first and third surveys (P < .001). Statistically significant improvement in body pain, general health, and work performance scores were noted as well (P < .05). CONCLUSION: The RELIEF stent eliminates VUR with similar stent-related morbidity and overall well-tolerance. RELIEF-associated USSQ scores were below published mean symptom scores for standard double-J stents and appear safe in this preliminary clinical trial.

Multi-scale statistical deformation based co-registration of prostate MRI and post-surgical whole mount histopathology.

BACKGROUND: Accurate delineations of regions of interest (ROIs) on multi-parametric magnetic resonance imaging (mpMRI) are crucial for development of automated, machine learning-based prostate cancer (PCa) detection and segmentation models. However, manual ROI delineations are labor-intensive and susceptible to inter-reader variability. Histopathology images from radical prostatectomy (RP) represent the "gold standard" in terms of the delineation of disease extents, for example, PCa, prostatitis, and benign prostatic hyperplasia (BPH). Co-registering digitized histopathology images onto pre-operative mpMRI enables automated mapping of the ground truth disease extents onto mpMRI, thus enabling the development of machine learning tools for PCa detection and risk stratification. Still, MRI-histopathology co-registration is challenging due to various artifacts and large deformation between in vivo MRI and ex vivo whole-mount histopathology images (WMHs). Furthermore, the artifacts on WMHs, such as tissue loss, may introduce unrealistic deformation during co-registration. PURPOSE: This study presents a new registration pipeline, MSERgSDM, a multi-scale feature-based registration (MSERg) with a statistical deformation (SDM) constraint, which aims to improve accuracy of MRI-histopathology co-registration. METHODS: In this study, we collected 85 pairs of MRI and WMHs from 48 patients across three cohorts. Cohort 1 (D1), comprised of a unique set of 3D printed mold data from six patients, facilitated the generation of ground truth deformations between ex vivo WMHs and in vivo MRI. The other two clinically acquired cohorts (D2 and D3) included 42 patients. Affine and nonrigid registrations were employed to minimize the deformation between ex vivo WMH and ex vivo T2-weighted MRI (T2WI) in D1. Subsequently, ground truth deformation between in vivo T2WI and ex vivo WMH was approximated as the deformation between in vivo T2WI and ex vivo T2WI. In D2 and D3, the prostate anatomical annotations, for example, tumor and urethra, were made by a pathologist and a radiologist in collaboration. These annotations included ROI boundary contours and landmark points. Before applying the registration, manual corrections were made for flipping and rotation of WMHs. MSERgSDM comprises two main components: (1) multi-scale representation construction, and (2) SDM construction. For the SDM construction, we collected N = 200 reasonable deformation fields generated using MSERg, verified through visual inspection. Three additional methods, including intensity-based registration, ProsRegNet, and MSERg, were also employed for comparison against MSERgSDM. RESULTS: Our results suggest that MSERgSDM performed comparably to the ground truth (p > 0.05). Additionally, MSERgSDM (ROI Dice ratio = 0.61, landmark distance = 3.26 mm) exhibited significant improvement over MSERg (ROI Dice ratio = 0.59, landmark distance = 3.69 mm) and ProsRegNet (ROI Dice ratio = 0.56, landmark distance = 4.00 mm) in local alignment. CONCLUSIONS: This study presents a novel registration method, MSERgSDM, for mapping ex vivo WMH onto in vivo prostate MRI. Our preliminary results demonstrate that MSERgSDM can serve as a valuable tool to map ground truth disease annotations from histopathology images onto MRI, thereby assisting in the development of machine learning models for PCa detection on MRI.

Green tea polyphenols causes cell cycle arrest and apoptosis in prostate cancer cells by suppressing class I histone deacetylases.

Green tea polyphenols (GTPs) reactivate epigenetically silenced genes in cancer cells and trigger cell cycle arrest and apoptosis; however, the mechanisms whereby these effects occur are not well understood. We investigated the molecular mechanisms underlying the antiproliferative effects of GTP, which may be similar to those of histone deacetylase (HDAC) inhibitors. Exposure of human prostate cancer LNCaP cells (harboring wild-type p53) and PC-3 cells (lacking p53) with 10-80 µg/ml of GTP for 24 h resulted in dose-dependent inhibition of class I HDAC enzyme activity and its protein expression. GTP treatment causes an accumulation of acetylated histone H3 in total cellular chromatin, resulting in increased accessibility to bind with the promoter sequences of p21/waf1 and Bax, consistent with the effects elicited by an HDAC inhibitor, trichostatin A. GTP treatment also resulted in increased expression of p21/waf1 and Bax at the protein and message levels in these cells. Furthermore, treatment of cells with proteasome inhibitor, MG132 together with GTP prevented degradation of class I HDACs, compared with cells treated with GTP alone, indicating increased proteasomal degradation of class I HDACs by GTP. These alterations were consistent with G(0)-G(1) phase cell cycle arrest and induction of apoptosis in both cell lines. Our findings provide new insight into the mechanisms of GTP action in human prostate cancer cells irrespective of their p53 status and suggest a novel approach to prevention and/or therapy of prostate cancer achieved via HDAC inhibition.

Serial prostate magnetic resonance imaging fails to predict pathological progression in patients on active surveillance.

INTRODUCTION: Limited data guide urological practice when employing prostate magnetic resonance imaging (MRI) in active surveillance (AS) protocols. To determine the ability of prostate MRI to predict pathological progression in AS patients, we correlated findings of serial MRI with results of surveillance biopsies. METHODS: Patients on AS with ≥2 prostate MRI and ≥2 prostate biopsies were included. Prostate Imaging-Reporting and Data System (PI-RADS) score upgrade, as assigned by experienced radiologists, was used to assess the ability of imaging to predict pathological biopsy progression. Imaging test statistics and the odds ratio of pathological progression according to MRI upgrade were calculated. RESULTS: Of 121 patients meeting criteria, 36 (30%) demonstrated MRI upgrade. Biopsy progression was noted in 55 patients (46%). Of these, 20 patients (37%) had biopsy progression predicted by MRI upgrade, while the remaining (n=35) had no lesion upgrade on prostate MRI. Conversely, among those with no biopsy progression (n=66), 16 patients (24%) had a false-positive upgrade on serial MRI. We report a sensitivity and specificity of MRI change for pathological progression of 36% and 76%, respectively. Although MRI change was associated with a positive predictive value of 56% for pathological progression, patients with a high-suspicion lesion (PI-RADS >3) at any time were more likely to experience disease progression, (odds ratio 3.3, 95% confidence interval 1.6-8.0, p<0.01). CONCLUSIONS: Given its modest sensitivity/specificity, serial prostate MRI should be used judiciously as a surveillance tool. However, when prostate MRI demonstrates a PI-RADS >3 lesion, a high index of suspicion should be maintained, as these patients are more likely to progress on AS.

Pre-surgical chronic kidney disease continues to drive outcomes in the modern era of minimally invasive renal surgery, despite advances in technology.

PURPOSE: To assess the impact of preoperative chronic kidney disease (CKD) on perioperative morbidity and mortality in a contemporary cohort undergoing renal surgery in an era of increased prevalence of minimally invasive surgery and partial nephrectomy. METHODS: The National Surgery Quality Improvement Program dataset was queried to identify patients undergoing radical nephrectomy (RN) or partial nephrectomy (PN) between 2010 and 2018. CKD staging was assigned based on creatinine clearance calculated using the Cockcroft-Gault formula. Multivariable logistic regression was performed to assess the effect of preoperative CKD stage on postoperative outcomes, including a composite variable encompassing multiple major complications. RESULTS: We analyzed 19,545 patients with CKD undergoing renal surgery. CKD stage ≥ 2 predicted an increase in major perioperative complications, OR 1.54 (95% CI 1.46-1.63); p < 0.01. The risk of perioperative morbidity increased linearly with increasing CKD stage. Patients with CKD stage > 2 also demonstrated increased 30-day mortality, OR 1.87 (95% CI 1.26-2.48); p < 0.01. Adjusting for surgery type, CKD staging predicted perioperative mortality in patients undergoing RN only, and perioperative morbidity in RN and PN. CONCLUSIONS: Here, we demonstrate a statistically significant increase in the risk of major postoperative complications following RN and PN with increasing CKD stage. Amongst patients undergoing RN, we also demonstrate increasing 30-day mortality with increasing CKD stage. Importantly, we highlight the ability of CKD staging to predict major perioperative outcomes with greater magnitude of effect than surgery type alone. Thus, we provide a model for translating CKD staging into operative risk amongst patients undergoing surgery for a renal mass.

Racial disparities in biochemical recurrence of prostate cancer.

BACKGROUND: The aim of this study was to determine the biochemical recurrence among Black and White American men with grade group 2-5 prostate cancer managed primarily by radical prostatectomy (RP). METHODS: This was a single-institution, retrospective study evaluating biochemical recurrence by self-identified race. 163 patients who underwent RP at the University Hospitals Cleveland Medical Center between 2015-2021 were analyzed for racial differences in age at diagnosis, clinical stage, and preoperative serum prostate-specific antigen (PSA). Patients were followed for PSA recurrence (PSA ≥ 0.2 ng/ml). Multivariate analysis was used to determine clinical and pathologic variables that were significant in predicting biochemical recurrence after RP and to determine whether race was an independent predictor of biochemical recurrence-free survival (BCRFS). RESULTS: Of 163 patients, 82 (50.3%) were Black Americans and 81 (49.7%) were White Americans with a median age of 62.7 ranging between 38.7 to 76.3 years. The grade-specific distribution of cancer 3+4 was 54.9% versus 65.4%; 4+3 was 25.6% versus 30.9%; 4+4 was 7.3% versus 2.5%; 4+5 was 12.2% versus 1.2% in Black American and White American men. Univariate analysis of BCRFS using Kaplan-Meier method demonstrated a significant difference among levels of Gleason score between Black Americans and White Americans (P = 0.041). Multivariable analysis after controlling the effects of age, Gleason score exhibited no significant difference of BCRFS comparing Black and White American men (P = 0.145). Specifically, the hazard of biochemical recurrence among Black Americans was 1.6 times (95% CI: 0.85-3.02) compared to White Americans (P = 0.145). CONCLUSION: Our study demonstrated a significant difference in BCRFS between Black and White American patients. Additional studies with larger sample size underlying this clinical disparity are warranted.

Testosterone deficiency in male organ transplant recipients.

Testosterone deficiency is known to affect men with increasing incidence throughout their lifespan. The clinical manifestations of testosterone deficiency, in turn, negatively impact men's quality of life and perception of overall health. The interaction of chronic systemic disease and androgen deficiency represent an area for potential intervention. Here, we explore the topic of testosterone deficiency amongst men with end-stage organ failure requiring transplantation in order to elucidate the underlying pathophysiology of androgen deficiency of chronic disease and discuss whether intervention, including testosterone replacement and organ transplantation, improve patients' outcomes and quality of life.

How Indian obese population managed their lifestyle during first and second lockdown during COVID-19 pandemic? - A comparative study.

Background: People from all over the world have been affected by the COVID-19 (SARS-CoV-2) pandemic. The lockdown during the pandemic has impacted the lifestyle of most of the population. The aim of the present study is to compare the effect of COVID lockdown-1 and lockdown-2 on the lifestyle of the obese Indian population. Methods: This was a cross-sectional study conducted during the COVID-19 lockdown on obese adults. A well-structured questionnaire was developed and administered among the study population. The study was conducted in two phases (lockdown-1 and lockdown-2). A total of 390 subjects were included in the study (260 subjects in the lockdown-1 phase and 130 subjects in the lockdown-2 phase). Data on diet, sleep, stress, and physical activity were obtained and analyzed. Results: The mean age of the participants of phase-1 in the study was 41.7 ± 10.2 years and the participants of phase-2 were 44.5 ± 9.2 years. Statistically significant differences were observed between lockdown-1 and lockdown-2 in terms of monitoring of weight and other comorbid conditions, changes in the consumption of refined flour and processed foods, sugar and sugar-sweetened foods, oils and ghee, duration of physical activity, changes in the duration of sleep, and the stress levels related to COVID-19 (P < 0.001). Conclusion: The impact of the lockdowns on health was very significant and different areas of lifestyle were affected in both the lockdowns. Weight gain was reported in both phases of the lockdown. The monitoring of health parameters, eating frequency, diet, and stress levels were affected during lockdown-1, whereas during lockdown-2, sleep duration and physical activity were affected. A comprehensive lifestyle modification plan is required to be developed to avoid these effects in the future.

Temporal improvements in renal surgery outcomes across surgical approaches.

PURPOSE: To evaluate patient outcomes in a contemporary cohort of patients undergoing partial nephrectomy (PN) or radical nephrectomy (RN). METHODS: The NSQIP database was used to identify patients undergoing PN or RN for renal neoplasms between 2010 and 2018. The SEER database was also queried to assess changes in tumor staging during the study period. Logistic regression was used to assess the independent relationship between surgery year and approach on postoperative complications. RESULTS: Between 2010 and 2018, NSQIP captured 58,020 cases, including 26,745 (46%) PN and 31,275 (54%) RN. The proportion of PN increased annually, from 39.8% in 2010 to 48.7% in 2018. This rise in PN coincided with a decrease in the proportion of patients experiencing complications, irrespective of surgical approach (20.4% of total cases to 14.2% of total cases). While limited by a lack of information on tumor characteristics, multivariable analysis controlling for patient characteristics demonstrated that RN was associated with an increased risk of complications, OR 1.42 (95% CI 1.35-1.49). CONCLUSION: Here, we report an 8.9% increase in the proportion of patients undergoing PN between 2010 and 2018, with no associated increase in perioperative morbidity/mortality. Given that there was no concurrent shift in stage or size of kidney tumors undergoing resection during the study period, these data therefore suggest markedly improved surgical technique and perioperative management nationally. Furthermore, the relative burden of complications has shifted from patients undergoing PN to those undergoing RN. Therefore PN, when technically feasible, should be increasingly considered.

Historical Considerations and Surgical Quality Improvement in Robotic Prostatectomy.

Laparoscopic prostatectomy was technically challenging and not widely adopted. Robotics led to the widespread adoption of minimally invasive prostatectomy, which has been used heavily, supplanting the open and traditional laparoscopic approach. The benefits of robotic prostatectomy are disputed. Data suggest that robotic prostatectomy outcomes have improved over time.

Bladder Agenesis and Bilateral Ectopic Ureters in an Infant Male With Cystic Renal Dysplasia, Imperforate Anus, and Penoscrotal Transposition.

Bladder agenesis is a rare congenital anomaly infrequently reported in the literature, with an incidence of 1/600,000 patients.1 Commonly associated with other fatal malformations, the condition is often incompatible with life.2 Prior reports estimate that over 90% of living children born with this malformation are female, owing to renal preservation resulting from low pressure drainage of urine into the vagina, uterus, and vestibule.3,4 Herein we report a rare case of an infant male born with penoscrotal transposition and end stage renal disease secondary to bilateral cystic renal dysplasia found to have concurrent bladder agenesis and bilateral ureteral ectopia.

Urologic Education in the Era of COVID-19: Results From a Webinar-Based Reconstructive Urology Lecture Series.

OBJECTIVE: To determine the response to a virtual educational curriculum in reconstructive urology presented during the COVID-19 pandemic. To assess learner satisfaction with the format and content of the curriculum, including relevance to learners' education and practice. MATERIALS AND METHODS: A webinar curriculum of fundamental reconstructive urology topics was developed through the Society of Genitourinary Reconstructive Surgeons and partnering institutions. Expert-led sessions were broadcasted. Registered participants were asked to complete a survey regarding the curriculum. Responses were used to assess the quality of the curriculum format and content, as well as participants' practice demographics. RESULTS: Our survey yielded a response rate of 34%. Survey responses showed >50% of practices offer reconstructive urologic services, with 37% offered by providers without formal fellowship training. A difference in self-reported baseline knowledge was seen amongst junior residents and attendings (P < .05). Regardless of level of training, all participants rated the topics presented as relevant to their education/practice (median response = 5/5). Responders also indicated that the curriculum supplemented their knowledge in reconstructive urology (median response = 5/5). The webinar format and overall satisfaction with the curriculum was highly rated (median response = 5/5). Participants also stated they were likely to recommend the series to others. CONCLUSION: We demonstrate success of an online curriculum in reconstructive urology. Given >50% of practices surveyed offer reconstruction, we believe the curriculum's educational benefits (increasing access and collaboration while minimizing the risk of in-person contact) will continue beyond the COVID-19 pandemic and that this will remain a relevant educational platform for urologists moving forward.

Tissue-Sparing Posterior Cervical Fusion With Interfacet Cages: A Systematic Review of the Literature.

STUDY DESIGN: Literature review. OBJECTIVES: Posterior cervical interfacet cages are an alternative to lateral mass fixation in patients undergoing cervical spine surgery. Recently, a percutaneous, tissue-sparing system for interfacet cage placement has been developed, however, there is limited clinical evidence supporting its widespread use. The aim was to review studies published on this system for patient reported outcomes, radiographic outcomes, intraoperative outcomes, and complications. METHODS: Four electronic databases (PubMed, EMBASE, Scopus, and MEDLINE) were queried for original published studies that evaluated the percutaneous, tissue-sparing technique for posterior cervical fusion with interfacet cage placement. All studies reporting on open techniques and purely biomechanical studies were excluded. RESULTS: The extensive literature search returned 7852 studies. After systematic review, a total of 7 studies met inclusion criteria. Studies were independently classified as retrospective or prospective cohort studies and each assessed by the GRADE criteria. Patient reported outcomes, radiographic outcomes, intraoperative outcomes, and complications were extracted from each study and presented. CONCLUSIONS: Tissue-sparing, posterior cervical fusion with interfacet cages may be considered a safe and effective surgical intervention in patients failing conservative management for cervical spondylotic disease. However, the quality of evidence in the literature is lacking, and controlled, comparative studies are needed for definitive assessment.

Accuracy of cortical bone trajectory screw placement in midline lumbar fusion (MIDLF) with intraoperative cone beam navigation.

BACKGROUND: Cortical bone trajectory (CBT) screws have been recently described as a method of lumbosacral fixation. These screws are typically inserted under fluoroscopic guidance with a medial-to-lateral trajectory in the axial plane and a caudal-to-cephalad trajectory in the sagittal plane. In an effort to reduce surgeon radiation exposure and improve accuracy, CBT screws may be inserted under navigation with intraoperative cone beam computed tomography (CT). However, the accuracy of CBT screw placement under intraoperative navigation has yet to be assessed in the literature. The purpose of the study was to evaluate the accuracy of CBT screw placement using intraoperative cone beam CT navigation. METHODS: One hundred and thirty-four consecutive patients who underwent CBT fixation with 618 screws under intraoperative navigation were analyzed from May 2016 through May 2018. Screws were placed by one of three senior spine surgeons using the Medtronic O-Arm Stealth Navigation. Screw position and accuracy were assessed on intraoperative and postoperative CT scans using 2D and 3D reconstructions with VitreaCore software. RESULTS: The majority of surgeries were primary cases (73.1%). The mean age at the time of surgery was 61.5±10.0 years and the majority of patients were female (61.2%). Most patients underwent surgery for a diagnosis of degenerative spondylolisthesis (47.8%) followed by mechanical collapse with foraminal stenosis (22.4%). Ten violations of the vertebral cortex were noted with an average breach distance of 1.0±0.7 mm. Three breaches were lateral (0.5%) and seven were medial (1.1%). The overall navigated screw accuracy rate was 98.3%. The accuracy to within 1 mm of error was 99.2%. There were no intra-operative neurologic, vascular, or visceral complications related to the placement of the CBT screws. CONCLUSIONS: CBT screw fixation under an intraoperative cone beam CT navigated insertion technique is safe and reliable. Despite five breaches greater than 1mm, there were no complications related to the placement of the CBT screws in this series.

Plant flavone apigenin: An emerging anticancer agent.

Research in cancer chemoprevention provides convincing evidence that increased intake of vegetables and fruits may reduce the risk of several human malignancies. Phytochemicals present therein provide beneficial anti-inflammatory and antioxidant properties that serve to improve the cellular microenvironment. Compounds known as flavonoids categorized anthocyanidins, flavonols, flavanones, flavonols, flavones, and isoflavones have shown considerable promise as chemopreventive agents. Apigenin (4', 5, 7-trihydroxyflavone), a major plant flavone, possessing antioxidant, anti-inflammatory, and anticancer properties affecting several molecular and cellular targets used to treat various human diseases. Epidemiologic and case-control studies have suggested apigenin reduces the risk of certain cancers. Studies demonstrate that apigenin retain potent therapeutic properties alone and/or increases the efficacy of several chemotherapeutic drugs in combination on a variety of human cancers. Apigenin's anticancer effects could also be due to its differential effects in causing minimal toxicity to normal cells with delayed plasma clearance and slow decomposition in liver increasing the systemic bioavailability in pharmacokinetic studies. Here we discuss the anticancer role of apigenin highlighting its potential activity as a chemopreventive and therapeutic agent. We also highlight the current caveats that preclude apigenin for its use in the human trials.

Intrarenal Injection of Escherichia coli in a Rat Model of Pyelonephritis.

Pyelonephritis is a bacterial infection of the kidney and is most commonly caused by Escherichia coli. Recurrent infections can cause significant renal inflammation and fibrosis ultimately resulting in declining kidney function. Before improved clinical management and prevention of pyelonephritis can be instituted, a reliable animal model must be established in order to study the mechanisms of progression, recurrence, and therapeutic efficacy. The transurethral infection model closely mimics human pyelonephritis but exhibits considerable variation due to its reliance on urethral reflux to transport the bacteria to the kidney. Herein, a detailed surgical protocol for performing bacterial injections into the rat renal pelvis is provided and confirmed by non-invasive Magnetic Resonance Imaging (MRI). Using this protocol, animals receive direct exposure to a desired concentration of E. coli bacteria and can fully recover from the surgical procedure with adequate post-operative care. This facilitates subsequent longitudinal MRI assessments of the experimental animal models for comparison with saline (sham) controls. Using this direct delivery approach, the severity of infection is controllable and applicable for mechanistic studies of progression as well as development of novel treatment strategies.