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Importance: It remains unclear whether diet may influence the risk of prostate cancer grade reclassification in men undergoing active surveillance., Objective: To assess the association of diet quality and dietary inflammatory potential with prostate cancer grade reclassification during active surveillance., Design, Setting, and Participants: This prospective cohort study included men diagnosed with grade group (GG) 1 prostate cancer from January 2005 to February 2017 who were undergoing active surveillance and at active surveillance enrollment prospectively completed a validated food frequency questionnaire regarding their usual dietary patterns. Data were analyzed from October 29, 2023, to June 17, 2024., Exposures: The Healthy Eating Index 1999-2000 (HEI) and energy-adjusted HEI (E-HEI) scores as a measure of adherence to the Dietary Guidelines for Americans and the Dietary Inflammatory Index (DII) and energy-adjusted DII (E-DII) scores as metrics of dietary inflammatory potential were calculated using self-reported diet data., Main Outcomes and Measures: A competing risk regression was performed to test the baseline HEI, E-HEI, DII, and E-DII scores for an association with grade reclassification to GG2 or greater or GG3 or greater (ie, extreme grade reclassification) during active surveillance, adjusting for established active surveillance prognostic factors and smoking history at baseline., Results: The study included 886 men (median age at diagnosis, 66 years [IQR, 61-69 years]). After median follow-up of 6.5 years (IQR, 4.0-9.1 years), 187 (21%) had grade reclassification to GG2 or greater, including 55 (6%) with extreme grade reclassification. The cumulative incidence of grade reclassification was 7% (95% CI, 5%-9%) at 3 years, 15% (95% CI, 12%-17%) at 5 years, and 33% (95% CI, 29%-37%) at 10 years; that of extreme grade reclassification was 2% (95% CI, 1%-4%) at 3 years, 4% (95% CI, 3%-5%) at 5 years, and 10% (95% CI, 7%-13%) at 10 years. Higher baseline HEI (subdistribution hazard ratio [SHR], 0.85; 95% CI, 0.73-0.98; P = .03) and E-HEI (SHR, 0.86; 95% CI, 0.74-1.00; P = .047) per 1-SD increase in score were associated with a significantly lower risk of grade reclassification. Higher baseline HEI (SHR, 0.72; 95% CI, 0.57-0.93; P = .01) and E-HEI (SHR, 0.73; 95% CI, 0.57-0.94; P = .01) per 1-SD increase in score were associated with a significantly lower risk of extreme grade reclassification. Neither the baseline DII nor E-DII was associated with either grade reclassification outcome (eg, for grade reclassification to ≥GG2, the SHR was 1.08 [95% CI, 0.93-1.26] per 1-SD increase in DII score and 1.02 [95% CI, 0.86-1.21] per 1-SD increase in E-DII score)., Conclusions and Relevance: The findings suggest that in men diagnosed with GG1 prostate cancer undergoing active surveillance, higher adherence to American dietary guideline recommendations may be associated with a lower risk of grade reclassification, particularly to GG3 or greater disease, which mandates curative treatment.

Purpose of Review: To describe patient experiences of transurethral resection of bladder tumor (TURBT) and review recent advances in enhancing clinical outcomes., Recent Findings: High rates of recurrence and progression of non-muscle invasive bladder tumors expose patients to multiple TURBT procedures throughout their disease process. Understanding the impact of TURBT on quality of life and patient experiences is crucial for shared decision-making, thus enhanced recovery protocol trials are being explored to improve patient outcomes. The variability in TURBT practices worldwide contributes to differing bladder tumor recurrence rates, prompting efforts to standardize practices by evaluating the impact of patient, hospital, and surgeon factors. For select cases, less intensive surveillance regimens have reduced toxicities and costs without compromising oncologic outcomes. New innovative approaches such as en bloc- and stratified resection techniques may reduce perioperative complications and improve clinical outcomes. Finally, neoadjuvant and ablative treatments have shown to be promising alternatives to TURBT, necessitating further investigation in this setting. TURBT is essential for diagnosing and treating bladder cancer. Reducing associated morbidities and improving surgical outcomes involve multifaceted approaches, including standardizing surgical practices, exploring innovative techniques, and optimizing surveillance regimens, all while promoting patient quality of life. Neoadjuvant therapies as alternative treatments are on the horizon and may ultimately change the landscape of bladder cancer care., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Deep learning (DL)-based algorithms to determine prostate cancer (PCa) Grade Group (GG) on biopsy slides have not been validated by comparison to clinical outcomes. We used a DL-based algorithm, AIRAProstate, to regrade initial prostate biopsies in 2 independent PCa active surveillance (AS) cohorts. In a cohort initially diagnosed with GG1 PCa using only systematic biopsies (n = 138), upgrading of the initial biopsy to ≥GG2 by AIRAProstate was associated with rapid or extreme grade reclassification on AS (odds ratio = 3.3, P = .04), whereas upgrading of the initial biopsy by contemporary uropathologist reviews was not associated with this outcome. In a contemporary validation cohort that underwent prostate magnetic resonance imaging before initial biopsy (n = 169), upgrading of the initial biopsy (all contemporary GG1 by uropathologist grading) by AIRAProstate was associated with grade reclassification on AS (hazard ratio = 1.7, P = .03). These results demonstrate the utility of a DL-based grading algorithm in PCa risk stratification for AS., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: To compare the clinical, economic, and health utility outcomes associated with alternative cystoscopic surveillance regimens for high-risk non-muscle-invasive bladder cancer (HRNMIBC)., Patients and Methods: We performed real-world clinical data-driven microsimulations of a hypothetical cohort of 100 000 patients diagnosed with HRNMIBC at age 70 years. The cohort was simulated to undergo alternative surveillance regimens recommended by five guidelines, and two hypothetical regimens-surveillance intensity escalation and de-escalation-which had a surveillance intensity moderately higher and lower, respectively, than the guideline-recommended regimens. We evaluated the 10-year cumulative incidence of muscle-invasive bladder cancer (MIBC), cancer-specific survival (CSS), overall survival (OS), and cost-effectiveness from a United States healthcare payer perspective., Results: The guideline-recommended surveillance regimens led to an estimated 10-year cumulative incidence of MIBC ranging from 11.0% to 11.6%, CSS 95.0% to 95.2%, and OS 69.7% to 69.8%. Surveillance intensity escalation resulted in a 10-year cumulative incidence of MIBC of 10.5% (95% confidence interval [CI] 10.3-10.7%), CSS of 95.4% (95% CI 95.2-95.5%), and OS of 69.9% (95% CI 69.6-70.1%), vs 11.9% (95% CI 11.7-12.1%), 94.9% (95% CI 94.8-95.1%), and 69.6% (95% CI 69.3-69.9%), respectively, from surveillance intensity de-escalation. By increasing surveillance intensity, the number-needed-to-treat to prevent one additional MIBC progression over 10 years was ≥80, and ≥257 to avoid one additional cancer-related mortality. Compared to surveillance intensity de-escalation, higher-intensity regimens incurred an incremental cost of ≥$336 000 per incremental quality-adjusted life year gained, which well exceeded conventional willingness-to-pay thresholds, ≥$686 000 per additional MIBC progression prevented, and ≥$2.2 million per additional cancer-related mortality avoided., Conclusion: In microsimulations testing a wide range of cystoscopic surveillance intensity for patients newly diagnosed with HRNMIBC, moderate surveillance de-escalation appears associated with an insignificant change in 10-year OS and furthermore is cost-effective vs higher-intensity surveillance regimens. These results suggest that moderate surveillance de-escalation can reduce costs of care without compromising life expectancy for many patients., (© 2024 BJU International.)

This study involved direct doping of In 2 O 3 into silicon carbide (SiC) powder, resulting in 8.0 at% In-doped SiC powder. Subsequently, heating at 500 °C was performed to form a target, followed by the utilization of electron beam (e-beam) technology to deposit the In-doped SiC thin films with the thickness of approximately 189.8 nm. The first breakthrough of this research was the successful deposition of using e-beam technology. The second breakthrough involved utilizing various tools to analyze the physical and electrical properties of In-doped SiC thin films. Hall effect measurement was used to measure the resistivity, mobility, and carrier concentration and confirm its n-type semiconductor nature. The uniform dispersion of In ions in SiC was as confirmed by electron microscopy energy-dispersive spectroscopy and secondary ion mass spectrometry analyses. The Tauc Plot method was employed to determine the Eg values of pure SiC and In-doped SiC thin films. Semiconductor parameter analyzer was used to measure the conductivity and the I-V characteristics of devices in In-doped SiC thin films. Furthermore, the third finding demonstrated that In 2 O 3 -doped SiC thin films exhibited remarkable current density. X-ray photoelectron spectroscopy and Gaussian-resolved spectra further confirmed a significant relationship between conductivity and oxygen vacancy concentration. Lastly, depositing these In-doped SiC thin films onto p-type silicon substrates etched with buffered oxide etchant resulted in the formation of heterojunction p-n junction. This junction exhibited the rectifying characteristics of a diode, with sample current values in the vicinity of 10 2 mA, breakdown voltage at approximately -5.23 V, and open-circuit voltage around 1.56 V. This underscores the potential of In-doped SiC thin films for various semiconductor devices.

A Cd-based metal-organic framework (Cd-MOF), named after {[Cd(ttc)(H 2 O)]·H 2 O} n (ttc = 1-imidazole-1-yl-2,4,6-benzene-tricarboxylic acid), was synthesized using the solvothermal reaction. The single-crystal structure was determined by single X-ray diffraction analysis, and crystalline characteristics and composition were confirmed by powder X-ray diffraction (PXRD) and thermogravimetric analysis (TG), respectively. Structural analysis showed that the Cd 2+ ion is in the seven-coordinated mode, in which ttc 2- ion adopts the μ 4 -η 1 -η 1 -η 2 -η 2 coordination mode. It is worth noting that the Cd 2+ ion is connected to ttc 2- to form a 2D network, and the adjacent 2D network is expanded into a 3D supramolecular network structure through weak hydrogen bonds. The fluorescence sensing experiments indicated that Cd-MOF could not only be used as a fluorescence sensor for Fe 3+ , fluazinam (FLU), and 2,4,6-trinitrophenolol (TNP) but also for sulfasalazine detection in aqueous solution. To verify the sensitivity of the fluorescent probe, we calculated its detection limit: 5.34 × 10 -8 M (Fe 3+ ), 7.8 × 10 -8 M (FLU), 1.21 × 10 -7 M (TNP), and 2.67 × 10 -7 M (SECT). In addition, the quenching mechanism was thoroughly studied., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Objectives: To compare the carbon footprint and environmental impact of single-use and reusable flexible cystoscopes., Materials and Methods: We analysed the expected clinical lifecycle of single-use (Ambu aScope™ 4 Cysto) and reusable (Olympus CYF-V2) flexible cystoscopes, from manufacture to disposal. Performance data on cumulative procedures between repairs and before decommissioning were derived from a high-volume multispecialty practice. We estimated carbon expenditures per-case using published data on endoscope manufacturing, energy consumption during transportation and reprocessing, and solid waste disposal., Results: A fleet of 16 reusable cystoscopes in service for up to 135 months averaged 207 cases between repairs and 3920 cases per lifecycle. Based on a manufacturing carbon footprint of 11.49 kg CO 2 /kg device for reusable flexible endoscopes and 8.54 kg CO 2 /kg device for single-use endoscopes, the per-case manufacturing cost was 1.37 kg CO 2 for single-use devices and 0.0017 kg CO 2 for reusable devices. The solid mass of single-use and reusable devices was 0.16 and 0.57 kg, respectively. For reusable devices, the energy consumption of reusable device reprocessing using an automated endoscope reprocessor was 0.20 kg CO 2 , and per-case costs of device repackaging and repair were 0.005 and 0.02 kg CO 2 , respectively. The total estimated per-case carbon footprint of single-use and reusable devices was 2.40 and 0.53 kg CO 2 , respectively, favouring reusable devices., Conclusion: In this lifecycle analysis, the environmental impact of reusable flexible cystoscopes is markedly less than single-use cystoscopes. The primary contributor to the per-case carbon cost of reusable devices is energy consumption of reprocessing., (© 2022 BJU International.)

Intramuscular injection of anemoside B4 (AB4) has a superior therapeutic effect on clinical mastitis in lactating cows. Here, we explored AB4's effect on milk whey in clinical mastitis-affected cows using proteomics. Among fifty clinical mastitis cows received AB4 administration (0.05 ml/kg/day, for 7 days), twelve healed cows were selected and marked as group T. Twelve clinically heathy cows received the same dose of saline for 7 days, marked as group C. Collected milk whey of group T before and after AB4 administration marked as T1 and T2, respectively. The milk whey of group C after saline injection marked as C1. Milk whey protein changes were detected using tandem mass tag-based quantitative proteomic. We identified 872 quantifiable proteins in the samples. Among them, 511 proteins between T1 and C1, and 361 proteins between T2 and T1 were significantly altered. T1 than C1 had significantly more proteins associated with inflammatory damage and trans-endothelial migration of leukocytes, whereas these proteins were reduced in T2 treated with AB4. Compared with C, proteins associated with fibrin clot degradation and complement system activation were downregulated in T1 but upregulated in T2. In summary, AB4 can exert its therapeutic effect on clinical mastitis in cows mainly by reducing inflammatory damage, activating the complement system, inhibiting trans-endothelial migration of leukocytes, and promoting degradation of milk fibrin clots., (© 2022. The Author(s).)

Placental extract has been used for skin care and delaying skin aging. Cow placenta is an abundant resource with a large mass, which has not been harnessed effectively. Cow placenta extract (CPE) has the functions of antioxidation, anti-inflammatory, promoting growth and development, and promoting hair growth. However, little is known about the effect of oral administration of cow placenta extract on skin conditions. Therefore, the present study aimed to investigate the antioxidant capacity of CPE in vitro and in vivo and its protective effect on d-galactose (D-gal) induced skin aging in mice. The results showed that CPE had strong free radical scavenging, reducing and metal chelating activities. CPE can increase the activity of catalase (CAT), glutathione peroxidase (GSH-Px), peroxidase (POD), superoxide dismutase (SOD), and the content of glutathione (GSH), decrease the content of malondialdehyde (MDA). Moreover, CPE can decrease the gene and protein expression of matrix metalloproteinase 1a (MMP-1a) and matrix metalloproteinase 3 (MMP-3) and increase the expression of transforming growth factor-β (TGF-β) and tissue inhibitor of metalloproteinase 1 (TIMP-1) of mouse skin. Histopathological analysis showed CPE reduced the collagen damage caused by D-gal, increased collagen synthesis and reduced its degradation to delay skin aging.

Purpose: Active surveillance (AS) with the possibility of delayed intervention (DI) is emerging as a safe alternative to immediate intervention for many patients with small renal masses (SRMs). However, limited comparative data exist to inform the most appropriate management strategy for SRMs., Materials and Methods: Decision analytic Markov modeling was performed to estimate the health outcomes and costs of 4 management strategies for 65-year-old patients with an incidental SRM: AS (with possible DI), immediate partial nephrectomy, radical nephrectomy, and thermal ablation. Mortality, direct medical costs, quality-adjusted life-years, and incremental cost-effectiveness ratios were evaluated over 10 years., Results: The 10-year all-cause mortality was 22.6% for AS, 21.9% for immediate partial nephrectomy, 22.4% for immediate radical nephrectomy, and 23.7% for immediate thermal ablation. At a willingness-to-pay threshold of $100,000/quality-adjusted life-year, AS was the most cost-effective management strategy. The results were robust in univariate, multivariate, and probabilistic sensitivity analyses. Clinical decision analysis demonstrated that the tumor's metastatic potential, patient age, individual preferences, and health status were important factors influencing the optimal management strategy. Notably, if the annual probability of metastatic progression from AS was sufficiently low (under 0.35%-0.45% for most ages at baseline), consistent with the typical metastatic potential of SRMs <2 cm, AS would achieve higher health utilities than the other strategies., Conclusions: Compared to immediate intervention, AS with timely DI offers a safe and cost-effective approach to managing patients with SRMs. For patients harboring tumors of very low metastatic potential, AS may lead to better patient outcomes than immediate intervention.

Background: For men on active surveillance (AS) for prostate cancer (PCa), disease progression and age-related changes in health may influence decisions about pursuing curative treatment., Objective: To evaluate the predicted PCa and non-PCa mortality at the time of reclassification among men on AS, to identify clinical criteria for considering a transition from AS to watchful waiting (WW)., Design, Setting, and Participants: Patients enrolled in a large AS program who experienced biopsy grade reclassification (Gleason grade increase) were retrospectively examined. All patients who had complete documentation of medical comorbidities at reclassification were included., Outcome Measurements and Statistical Analysis: A validated model was used to assess 10- and 15-yr untreated PCa and non-PCa mortalities based on patient comorbidities and PCa clinical characteristics. We compared the ratio of predicted PCa mortality with predicted non-PCa mortality ("predicted mortality ratio") and divided patients into four risk tiers based on this ratio: (1) tier 1 (ratio: >0.33), (2) tier 2 (ratio 0.33-0.20), (3) tier 3 (ratio 0.20-0.10), and (4) tier 4 (ratio <0.10)., Results and Limitations: Of the 344 men who were reclassified, 98 (28%) were in risk tier 1, 85 (25%) in tier 2, 93 (27%) in tier 3, and 68 (20%) in tier 4 for 10-yr mortality. Fifteen-year risk tiers were distributed similarly. The 23 (6.7%) men who met the "transition triad" (age >75 yr, Charlson Comorbidity Index >3, and grade group ≤2) had a 14-fold higher non-PCa mortality risk and a lower predicted mortality ratio than those who did not (0.07 vs 0.23, p < 0.001). The primary limitations of our study included its retrospective nature and the use of predicted mortalities., Conclusions: At reclassification, nearly half of patients had a more than five-fold and one in five patients had a more than ten-fold higher risk of non-PCa death than patients having a risk of untreated PCa death. Despite a more significant cancer diagnosis, a transition to WW for older men with multiple comorbidities and grade group <3 PCa should be considered., Patient Summary: Men with favorable-risk prostate cancer and life expectancy of >10 yr are often enrolled in active surveillance, which entails delay of curative treatment until there is evidence of more aggressive disease. We examined a group of men on active surveillance who developed more aggressive disease, and found, nevertheless, that the majority of these men continued to have a dramatically higher risk of death from non-prostate cancer causes than from prostate cancer based on a risk prediction tool. For men older than 75 yr, who have multiple medical conditions and who do not have higher-grade cancer, it may be reasonable to reconsider the need for curative treatment given the low risk of death from prostate cancer compared with the risk of death from other causes., (Copyright © 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

A technique using the single-string, closed-loop fixation method to reposit dislocated triple-looped haptic intraocular lens (IOL)-capsular bag complex is described. The long needle or curved needle with a 10-0/8-0 polypropylene suture and a 27/30-gauge needle were used as the guide needle to pass through the fenestrated haptics twice. The scleral interlaminar course was used as the fixed point. Last, a fixation knot was created in the sclerotomy by the 2 ends of the thread to close the suture loop for IOL fixation. Another knot was created about 2 to 3 mm from the exit point and was intrasclerally anchored by the aid of the attached needle. 4 eyes from 4 consecutive patients were studied retrospectively; during all follow-up visits, the IOLs were well centered and stable, and no suture erosion, hypotony, scleral atrophy, chronic inflammation, retinal tears, and/or detachments were observed., (Copyright © 2022 Published by Wolters Kluwer on behalf of ASCRS and ESCRS.)

Objective: Judicious opioid stewardship would match each patient's prescription to their true medical necessity. However, most prescribing paradigms apply preset quantities and clinical judgment without objective data to predict individual use. We evaluated individual patient and in-hospital parameters as predictors of post-discharge opioid utilization after radical prostatectomy (RP) to provide evidence-based guidance for individualized prescribing., Methods: A prospective cohort of patients who underwent open or robotic RP were followed in the Opioid Reduction Intervention for Open, Laparoscopic, and Endoscopic Surgery (ORIOLES) initiative. Baseline demographics, in-hospital parameters, and inpatient and post-discharge pain medication utilization were tabulated. Opioid medications were converted to oral morphine equivalents (OMEQ). Predictive factors for post-discharge opioid utilization were analyzed by univariable and multivariable linear regression, adjusting for opioid reduction interventions performed in ORIOLES., Results: Of 443 patients, 102 underwent open and 341 underwent robotic RP. The factors most strongly associated with post-discharge opioid utilization included inpatient opioid utilization in the final 12 hours before discharge (+39.6 post-discharge OMEQ if inpatient OMEQ was >15 vs. 0), maximum patient-reported pain score (range 0-10) in the 12 hours before discharge (+27.6 OMEQ for pain score ≥6 vs. ≤1), preoperative opioid use (+76.2 OMEQ), and body mass index (BMI; +1.4 OMEQ per 1 kg/m 2 ). A final predictive calculator to guide post-discharge opioid prescribing was constructed., Conclusions: Following RP, inpatient opioid use, patient-reported pain scores, prior opioid use, and BMI are correlated with post-discharge opioid utilization. These data can help guide individualized opioid prescribing to reduce risks of both overprescribing and underprescribing., Competing Interests: Conflicts of interest The authors have no relevant competing interests to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: This study evaluated the utility of self-reported quality of life (QOL) metrics in predicting mortality among all-comers with renal cell carcinoma (RCC) and externally tested the findings in a registry of patients with small renal masses., Methods: The Surveillance, Epidemiology, and End Results-Medicare Health Outcomes Survey (SEER-MHOS) captured QOL metrics composed of mental component summary (MCS) and physical component summary (PCS) scores. Regression models assessed associations of MCS and PCS with all-cause, RCC-specific, and non-RCC-specific mortality. Harrell's concordance statistic (the C-index) and the Akaike information criterion (AIC) determined predictive accuracy and parsimony, respectively. Findings were tested in the prospective Delayed Intervention and Surveillance for Small Renal Masses (DISSRM) registry., Results: In SEER-MHOS, 1494 patients had a median age of 73.4 years and a median follow-up time of 5.6 years. Each additional MCS and PCS point reduced the hazard of all-cause mortality by 1.3% (95% CI, 0.981-0.993; P < .001) and 2.3% (95% CI, 0.971-0.984; P < .001), respectively. Models with QOL metrics demonstrated higher predictive accuracy (C-index, 72.3% vs 70.1%) and parsimony (AIC, 9376.5 vs 9454.5) than models without QOL metrics. QOL metrics exerted a greater effect on non-RCC-specific mortality than RCC-specific mortality. External testing in the DISSRM registry confirmed these findings with similar results for all-cause mortality., Conclusions: Models with self-reported QOL metrics predicted all-cause mortality in patients with RCC with higher accuracy and parsimony than those without QOL metrics. Physical health was a stronger predictor of mortality than mental health. The findings support the incorporation of QOL metrics into prognostic models and patient counseling for RCC., (© 2021 American Cancer Society.)

Purpose: To evaluate the total cost of outpatient flexible cystoscopy associated with reusable device purchase, maintenance, and reprocessing, and to assess potential cost benefits of single-use flexible cystoscopes., Methods: Cost data regarding the purchasing, maintaining, and reprocessing of reusable flexible cystoscopes were collected using a micro-costing approach at a high-volume outpatient urology clinic. We estimated the costs to facilities with a range of annual procedure volumes (1000-3000) performed with a fleet of cystoscopes ranging from 10 to 25. We also compared the total cost per double-J ureteral stent removal procedure performed using single-use flexible cystoscopes versus reusable devices., Results: The cost associated with reusable flexible cystoscopes ranged from $105 to $224 per procedure depending on the annual procedure volume and cystoscopes available. As a practice became more efficient by increasing the ratio of procedures performed to cystoscopes in the fleet, the proportion of the total cost due to cystoscope reprocessing increased from 22 to 46%. For ureteral stent removal procedures, the total cost per procedure using reusable cystoscopes (range $165-$1469) was higher than that using single-use devices ($244-$420), unless the annual procedure volume was sufficiently high relative to the number of reusable cystoscopes in the fleet (≥ 350 for a practice with ten reusable cystoscopes, ≥ 700 for one with 20 devices)., Conclusion: The cost of reprocessing reusable cystoscopes represents a large fraction of the total cost per procedure, especially for high-volume facilities. It may be economical to adopt single-use cystoscopes specifically for stent removal procedures, especially for lower-volume facilities., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Cancer-specific survival for men with clinical stage I (CSI) seminoma approaches 100%, regardless of the management approach chosen after orchiectomy. Given the young age and high survival rate of these patients, there has been a shift toward minimizing treatment-related morbidity and cost. In this context, non-risk-adapted active surveillance (NRAS) has emerged as a desirable management strategy., Objective: To evaluate the clinical, quality of life, and economic values of postorchiectomy NRAS for CSI seminoma., Design, Setting, and Participants: We developed a decision analytic Markov model to estimate the costs and health outcomes of competing postorchiectomy management strategies for otherwise healthy 30-yr-old men with CSI seminoma., Intervention: Real-world current practice, comprising active surveillance and adjuvant therapies (reference arm), was compared with empiric adjuvant radiotherapy (option 1), empiric adjuvant chemotherapy (option 2), risk-adapted active surveillance (RAAS; option 3), and NRAS (option 4)., Outcome Measurements and Statistical Analysis: Quality-adjusted life-years (QALYs), medical costs, incremental cost-effectiveness ratio, mortality, and unnecessary treatment avoidance were estimated over a 10-yr period. Uncertainties in model input values were accounted for using univariate, scenario, and probabilistic sensitivity analyses., Results and Limitations: NRAS dominated all other management options, offering the lowest per-patient health care cost ($3839) and the highest QALYs gained (7.74) over 10 yr. On probabilistic sensitivity analysis, NRAS had the highest chance of being most cost effective. Although NRAS resulted in the highest rate of salvage chemotherapy (20% vs 6% radiotherapy, 6% chemotherapy, 15% current practice, and 16% RAAS), it had the same mortality rate compared to current practice (2.5%). NRAS also allowed 80% of patients to avoid unnecessary treatment compared with 46% for current practice and 52% for RAAS. Study limitations included model simplifications, model parameter assumptions, as well as the absence of patient preference as a decision factor., Conclusions: NRAS maintains high cure rates for CSI seminoma, minimizes unnecessary treatment, and is cost effective compared with other management strategies., Patient Summary: Clinical stage I (CSI) seminoma is one of the most common forms of testicular cancer. Surgery is the first step in the treatment of men with this disease, and some men may receive additional treatment with radiation or chemotherapy afterward. As most men are cured with surgery alone, non-risk-adapted active surveillance (NRAS), which involves routine monitoring with imaging and blood tests for disease recurrence after surgery, has become a desirable treatment option. Our study shows that in addition to maintaining high survival rates and avoiding unnecessary radiation and chemotherapy, NRAS is cost effective for the health care system., (Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Incidentally detected small renal masses (SRMs) may be one of several benign or malignant tumor histologies, and are heterogeneous in oncologic potential. Renal mass biopsy can be used to determine the histology of SRMs. However, this invasive approach has significant limitations. Technetium-99m sestamibi single photon emission computed tomography/computed tomography ( 99m Tc-sestamibi SPECT/CT) is a promising imaging tool that can aid in identifying benign renal oncocytomas and hybrid oncocytic/chromophobe tumors., Objective: To evaluate the clinical and economic value of 99m Tc-sestamibi SPECT/CT in guiding the management of SRMs., Design, Setting, and Participants: We developed a decision analysis model to estimate the costs and health outcomes of competing management strategies for a healthy 65-yr-old patient with an asymptomatic SRM., Intervention: Empiric surgery (reference); real-world clinical practice (RWCP) consisting of empiric surgery, thermal ablation, and active surveillance (alternative reference); renal mass biopsy (option 1); 99m Tc-sestamibi SPECT/CT (option 2); and 99m Tc-sestamibi SPECT/CT followed by biopsy to confirm benign SRMs (option 3)., Outcome Measurements and Statistical Analysis: We assessed lifetime health utilities, measured in quality-adjusted life years (QALYs), and direct medical costs from a health payer perspective. We calculated the incremental cost-effectiveness ratio (ICER) for options 1-3 versus the reference and alternative reference arms, with a willingness-to-pay threshold of $50 000/QALY. Univariate, multivariate, and probabilistic sensitivity analyses were performed., Results and Limitations: Option 3 had a very low risk of untreated malignant tumors (0.2%, vs 2.1% for option 1, 4.2% for option 2, and 0% for empiric surgery) and the highest probability of leaving benign tumors untreated (84.4%, vs 53.9% for option 1, 51.7% for option 2, and 0% for empiric surgery). Option 3 dominated empiric surgery and options 1 and 2 (ie, lower costs and higher QALYs). Compared with RWCP, options 1-3 were all cost effective; option 3 had the lowest ICER of $18 821/QALY. These findings were robust to alternative input values. Study limitations included data uncertainties and a limited number of centers from which 99m Tc-sestamibi SPECT/CT performance data were collected., Conclusions: 99m Tc-sestamibi SPECT/CT followed by confirmatory biopsy helps avoid surgery for benign SRMs, minimizes untreated malignant SRMs, and is cost effective compared with existing strategies., Patient Summary: Our research suggests that by using a noninvasive imaging test, known as technetium-99m sestamibi single photon emission computed tomography/computed tomography, to diagnose small renal masses, urologists may avoid unnecessary surgery for benign tumors and minimize the risk of leaving a malignant tumor untreated. Moreover, the use of this strategy to diagnose small renal masses is cost effective for the health care system., (Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To review the current literature on quality of care in the diagnosis and management of early-stage testicular cancer., Methods: PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched for studies on quality of care in testicular cancer diagnosis and management from January 1980 to August 2018. Major overlapping themes related to quality of care in the diagnosis and management of TGCT were identified and evidence related to these themes were abstracted., Evidence: 62 studies were included in the review. A number of themes were identified including (1) trends in survival and outcomes, (2) management patterns, (3) adherence to evidence-based clinical guidelines, (4) delays in care, (5) treatment complications and toxicities, (6) sociodemographic factors, (7) volume of patients treated, (8) gaps in provider knowledge and medical errors, and (9) multidisciplinary approaches to care., Evidence Summary: As survival for patients with testicular cancer improves, there has been a greater emphasis on other components of quality of care, such as reducing treatment toxicity and minimizing delays in diagnosis. Efforts to meet these goals include encouragement of adherence to evidence-based guidelines, greater utilization of surveillance, and promotion of multidisciplinary team-based care. Although outcomes have improved, social determinants of health, such as insurance status, race, and geographical residence all may influence survival and cancer-related outcomes. Additionally, qualitative review indicates patients who receive care at high-volume institutions appear to experience better outcomes than those treated at smaller centers., Conclusions: As outcomes and survival improve for patients with testicular cancer, quality of care has become an important consideration. Future avenues of research on this topic include identifying an appropriate balance between centralization of care and expanding access to underserved areas, minimizing delays in care, ensuring greater adherence to clinical guidelines, and addressing sociodemographic and racial disparities in outcomes., (Copyright © 2021. Published by Elsevier Inc.)

Purpose: To evaluate the association of post-RP drain placement with post-operative complications and opioid use at a high-volume institution., Methods: A prospective, comparative cohort study of patients undergoing robot-assisted or open RP was conducted. Patients for two surgeons did not routinely receive pelvic drains ("No Drain" arm), while the remainder routinely placed drains ("Drain" arm). Outcomes were evaluated at 30 days including Clavien-Dindo complications and opioid use. Intention-to-treat primary analysis and additional secondary analyses were performed using appropriate statistical tests and logistic regression., Results: Of 498 total patients, 144 (28.9%) were in the No Drain arm (all robot-assisted) and 354 (71.1%) in the Drain arm. In the No Drain arm, 19 (13.2%) intraoperatively were chosen to receive drains. There was no difference in overall or major (Clavien ≥ 3) complications between groups (p = 0.2 and 0.4, respectively). Drain deferral did not predict complications on multivariable analysis adjusted for age, BMI, comorbidities, clinical risk, surgical approach, operating time, lymphadenectomy, and number of nodes removed [OR 0.61, 95% CI 0.34-1.11, p = 0.10]; nor did it predict symptomatic fluid collection, adjusting for lymphadenectomy and nodes removed [OR 1.14, 95% CI 0.43-3.60, p = 0.8]. Drain deferral did not decrease opioid use (p = 0.5). Per protocol analysis and restriction to robot-assisted cases demonstrated similar results., Conclusion: There was no difference in adverse events, complications, symptomatic collections, or opioid use with deferral of routine drain placement after RP. Experienced surgeons may safely defer drain placement in the majority of robot-assisted RP cases.

Objective: To evaluate perioperative complications for open radical prostatectomy (ORP) and robot-assisted RP (RARP) for patients enrolled in the PREvention of VENous ThromboEmbolism Following Radical Prostatectomy (PREVENTER; ClinicalTrials.gov Identifier: NCT03006562) trial, to determine predictors and impact on opioid consumption., Patients and Methods: A prospective cohort of 500 patients undergoing ORP and RARP was followed to determine rates of complications and opioid use. Complications were classified 30 days after RP using the Clavien-Dindo system. Patient characteristics and outcomes were compared using appropriate statistical tests. Logistic and linear regressions were performed to identify predictors of complications and evaluate the relationship between complications and postoperative opioid use., Results: A total of 124 (24.8%) men underwent ORP and 376 (75.2%) RARP, with 418 (83.6%) receiving pelvic lymph node dissection (PLND). While 83 patients (16.6%) had complications, only 19 (3.8%) were major (Clavien-Dindo Grade ≥III), with no differences by surgical approach. PLND (odds ratio [OR] 2.96, 95% confidence interval [CI] 1.25-8.71; P = 0.03) and Stage pT3b (OR 2.76, 95% CI 1.23-6.00;P = 0.01) were the only predictors of complications after controlling for potential confounders. Patients who had complications had greater inpatient (P = 0.02) and outpatient (P = 0.005) opioid use, which persisted after controlling for patient-reported pain, attending surgeon variation, surgical approach, and undergoing PLND (inpatient β:77.2, 95% CI 17.9-136.5,P = 0.03; and outpatient β:21.9, 95% CI 4.7-39.1,P = 0.01)., Conclusion: In an analysis of prospectively collected data, overall and major complications rates did not differ by surgical approach. Patients receiving PLND and with Stage pT3b disease had more complications. Complications were independently associated with higher inpatient and outpatient postoperative opioid use., (© 2020 The Authors BJU International © 2020 BJU International Published by John Wiley & Sons Ltd.)

Objective: To perform an early comparative study of outcomes between single-port and robot-assisted laparoscopic radical prostatectomy (SP-RALRP) and standard RALRP at our institution and pooled analysis of series to date., Patients and Methods: Patients with organ-confined prostate cancer undergoing SP-RALRP at a high-volume institution were identified retrospectively along with reported SP-RALRP series to date. Data were compared to a contemporary prospective cohort of men undergoing standard RALRP. Patient demographics, perioperative and postoperative data, and complications categorized by the Clavien-Dindo system were compared for the institutional and pooled SP-RALRP cohorts to standard RALRP., Results: A total of 208 SP-RALRP cases were identified (26 from our institution) and compared to 376 standard RALRP cases. In the institutional analysis, there was no difference in operative time, length of stay, overall complications (15.4% vs 17.3%, P= 1.0), major (Clavien ≥III) complications (3.8% vs 3.7%, P = .6), inpatient opioid use, or patient-reported pain scores; median estimated blood loss (100 mL vs 150 mL, P = .02) and number of lymph nodes removed (5.5 vs 9, P = .002) were lower for SP-RALRP. In the pooled analysis, 208 patients receiving SP-RALRP had similar estimated blood loss and complication rates but fewer lymph nodes removed (P = .02) and marginally longer operating time (+16 minutes, P = .01) compared to standard RALRP. The difference in rate of positive surgical margins was not statistically significant (31.3% vs 24.5%, P = .08)., Conclusion: Based on an early experience with SP-RALRP at a high-volume center and a pooled analysis of SP series to date, perioperative and pathologic outcomes appear nearly equivalent compared to standard RALRP., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: This study aimed to determine the effect of parathyroid hormone-related protein (PTHrP) on proliferation of cardiac fibroblasts (CFs) in primary cultures of neonatal Wistar rats., Methods: Different PTHrP concentrations were added to CFs of neonatal Wistar rats and the cells were grouped according to the concentrations added. A verapamil (VPL) group and a calcitriol (CAL) group were also established. Changes in cell proliferation and in cyclic adenosine monophosphate and calcium ion levels were identified and recorded., Results: We found that as the concentration of PTHrP increased, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT, a tetrazolium salt) colorimetric absorbance values (A values) decreased. These values in the PTHrP groups were significantly lower than those in the control group. MTT colorimetric A values and 3 H-thymidine deoxyribose intake were lower in the VPL group, low-dose CAL group, and the PTHrP 10 -7 mol/L group compared with the control group. However, MTT colorimetric A values and 3 H-thymidine deoxyribose intake were higher in the high-dose CAL group than in the PTHrP 10 -7 mol/L group. As PTHrP concentrations increased, intracellular cyclic adenosine monophosphate concentrations also increased., Conclusion: PTHrp, VPL, and low-dose CAL inhibit proliferation of CFs, while high-dose CAL promotes proliferation of CFs.

Purpose of Review: We conducted a review of the literature describing the most up-to-date diagnosis and treatment options of chronic bacterial prostatitis., Recent Findings: Recurrence after oral antimicrobial therapy is common, due in part to the rising rates of antimicrobial resistance and inability to completely clear the offending bacteria from the prostate following prostatitis. Recent literature has described various treatment options for chronic bacterial prostatitis refractory to conventional antimicrobial agents, including the use of alternative agents such as fosfomycin, direct antimicrobial injections into the prostate, surgical removal of infected prostatic tissue, chronic oral antibiotic suppression, and an emerging novel therapy utilizing bacteriophages to target antibiotic resistant bacteria. Management of chronic bacterial prostatitis, especially recurrence after oral antimicrobial treatment, remains challenging. This review highlights an urgent need for further evidence assessing the efficacy and safety of treatment modalities for chronic bacterial prostatitis refractory to conventional oral antimicrobials.

Background: A proportion of men with grade group (GG) 2 intermediate risk (IR) prostate cancer are downgraded to GG1 or harbor favorable pathology (FP, defined as GG1 or GG2 with <5% Gleason pattern 4) at radical prostatectomy (RP). Prediction of downgrading or FP may help identify potential active surveillance candidates within this group that have outcomes similar to biopsy low-risk (LR) disease., Methods: We performed a comparative cohort study of biopsy LR and IR men who underwent RP at The Johns Hopkins Hospital and Bayview Medical Center between 2005 and 2018. We evaluated pathological outcomes at RP and recurrence-free survival (RFS). Multivariable logistic regression and Cox proportional hazards regression were applied and individual predicted probabilities were calculated., Results: Among 2943 biopsy GG2 IR patients, 223 (7.6%) were downgraded to GG1, while 525 (17.8%) had FP; 730 of 1325 biopsy LR patients (55.1%) were upgraded (GG >1). Concordance statistics for final predictive regression models were 0.76 for downgrading and 0.70 for upgrading. Biopsy GG2 IR patients downgrading to GG1 or harboring FP had similar RFS to biopsy LR patients. A cutoff of >10% predicted probability of downgrading (24.7% of patients; hazard ratio [HR], 1.55; 95% CI, 0.89-2.68) or >20% predicted probability of FP (37.0% of patients; HR, 1.35; 95% CI, 0.81-2.24) led to similar RFS to biopsy LR patients., Conclusion: GG2 IR patients who experience downgrading or harbor FP had similar oncologic outcomes as LR patients. The developed models may serve as tools to inform patients about the risks of pathological downgrading/upgrading and help identify a segment of GG2 IR patients who would consider pursuing active surveillance based on predicted probability cutoffs., (© 2020 American Cancer Society.)

Objective: The objective of this study was to assess the validity of the Cornerstone Diabetes Simulation (CDS), a Microsoft Excel ® -based patient-level simulation for type 2 diabetes mellitus based on risk equations from the revised United Kingdom Prospective Diabetes Study Outcomes Model (UKPDS-OM2, also known as UKPDS 82)., Methods: Three levels of validation were conducted. Internal validation was assessed through independent review and model stress-testing. External validation was addressed by populating the CDS with baseline characteristics and treatment effects from three major diabetes clinical trials used in the Fifth Mount Hood Diabetes Challenge (MH5) for computer simulation models. Cross-validation of predicted outcomes was tested versus eight models that participated in the MH5. Simulated results were compared with observed clinical outcomes via the coefficient of determination (R 2 ) for both the absolute risk of each clinical outcome and the difference in absolute risk between control and intervention arm in each trial. We ensured transparency of all model inputs and assumptions in reporting., Results: The CDS could be used to predict 18 of 39 single and composite endpoints across the three trials. The model obtained an R 2 of 0.637 for predicted versus observed absolute risks, and an R 2 of 0.442 for predicted versus observed risk differences between control and intervention. Among the other eight models, only one obtained a higher R 2 value under both definitions, albeit based on only four predicted endpoints., Conclusions: The CDS provides good predictions of diabetes-related complications when compared to observed trial outcomes and previously validated models. The model has value as a validated tool in cost-effectiveness evaluations.

Objective: To determine whether use of renal mass biopsy may be associated with a reduction in surgery for patients with small, localized renal cell carcinoma (cT1aN0M0), especially among older patients and patients with greater comorbidity burden., Methods: A total of 106,258 patients with cT1aN0M0 renal cell carcinoma from 2004 to 2015 were analyzed in the National Cancer Data Base. Multivariable logistic regression identified independent associations with nonsurgical management, receipt of biopsy, and pathologic upstaging. Marginal effects were derived by age and comorbidity. A sensitivity analysis was conducted in years identifying patients undergoing active surveillance (2010-2015)., Results: There was increased use of biopsy (8.0%-15.3%) and nonsurgical management (11.7%-15.6%) over time. Biopsy was significantly associated with use of nonsurgical management (OR 4.80 [95%CI 4.58-5.02], P <.001) as well as active surveillance (OR 1.87 [1.69-2.07], P <.001) in the sensitivity analysis. Individual predicted probability of undergoing nonsurgical management ranged from 3% to 92% (median 31.4% with use of biopsy) and increased with age and comorbidity. Pathologic tumor upstaging (≥pT3a) occurred more frequently for patients receiving biopsy compared to no biopsy (5.8% vs 3.3%, P <.001). After adjustment, biopsy remained a statistically significant predictor of upstaging (OR 1.31 [95%CI 1.24-1.38], P <.001)., Conclusion: Overall, biopsy demonstrated a strong, independent association with reduced use of surgery for cT1aN0M0 kidney cancer, especially with increasing age and comorbidity. The potential association of renal mass biopsy with upstaging warrants caution, but it is uncertain whether it impacts prognosis relative to true perinephric fat invasion., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: To identify trends in physician drug prescribing practices for sickle cell disease (SCD)., Methods: We used data from the National Disease and Therapeutic Index to evaluate medications prescribed to children (definition: aged 19 years or younger) and adults (20 years or older) with SCD by office-based physicians in the United States during 1997 to 2017. Prescriptions were evaluated in 3-year intervals., Results: The proportion of SCD visits that included new/continued hydroxyurea prescriptions increased from less than or equal to 8% before 2009 to 33% in 2015 to 2017. The increase was significant in visits by children (2.5% in 1997-1999 to 47% in 2015-2017; P = .003 by Spearman's rank-order correlation) but not in adults (6.9% to 11%; P = .12). Opioids, started/continued in 13% (lowest 3-year average) to 35% (highest) of visits by children and 55% to 81% of visits by adults, remained the most frequently prescribed medications for SCD overall. There were no significant changes over time in opioid prescribing for adults (P = .64) or children (P = .38). Hematologists/oncologists accounted for a higher proportion of visits by children (67.2% over 1997-2017) than adults (25.2%), while emergency medicine visits were higher in adults (14.0%) than children (2.6%)., Conclusions: This study suggests a robust increase in hydroxyurea prescribing for children with SCD. The BABY HUG trial, which demonstrated safety and efficacy of starting hydroxyurea in infancy and informed current SCD guidelines recommending broader use in children, may have contributed to this increase. However, hydroxyurea prescribing for adults remains infrequent and considerably lower than opioids. Barriers in access to specialist care persist for adults with SCD., (© 2019 John Wiley & Sons, Ltd.)

Microwave-induced learning and memory deficits in animal models have been gaining attention in recent years, largely because of increasing public concerns on growing environmental influences. The data from our group and others have showed that the injury of mitochondria, the major source of cellular adenosine triphosphate (ATP) in primary neurons, could be detected in the neuron cells of microwave-exposed rats. In this study, we provided some insights into the cellular and molecular mechanisms behind mitochondrial injury in PC12 cell-derived neuron-like cells. PC12 cell-derived neuron-like cells were exposed to 30 mW/cm(2) microwave for 5 min, and damages of mitochondrial ultrastructure could be observed by using transmission electron microscopy. Impairments of mitochondrial function, indicated by decrease of ATP content, reduction of succinate dehydrogenase (SDH) and cytochrome c oxidase (COX) activities, decrease of mitochondrial membrane potential (MMP), and increase of reactive oxygen species (ROS) production, could be detected. We also found that hypoxia-inducible factor-1 (HIF-1α), a key regulator responsible for hypoxic response of the mammalian cells, was upregulated in microwave-exposed neuron-like cells. Furthermore, HIF-1α overexpression protected mitochondria from injury by increasing the ATP contents and MMP, while HIF-1α silence promoted microwave-induced mitochondrial damage. Finally, we demonstrated that both ERK and PI3K signaling activation are required in microwave-induced HIF-1α activation and protective response. In conclusion, we elucidated a regulatory connection between impairments of mitochondrial function and HIF-1α activation in microwave-exposed neuron-like cells. By modulating mitochondrial function and protecting neuron-like cells against microwave-induced mitochondrial injury, HIF-1α represents a promising therapeutic target for microwave radiation injury.

Objective: To study the micromeritic properties of different particle size of Scutellaria baicalensis and provide a basis for being directly used or as raw material of Chinese herba preparation., Methods: Size distribution, surface area and pore volume, contact angle, angle of repose and bulk density, moisture absorption, micromorphology, Infrared spectrum, HPLC fingerprint were used to evaluate the differences of micromeritic properties of 4 kinds of Scutellaria baicalensis superfine grinding., Results: With the particle size of powders decreased, size distribution and bulk density decreased, the surface area and pore volume, contact angle and moisture absorption increased, angle of repose first increased and then decreased. Infrared spectrum and HPLC fingerprint showed no change of chemical composition of Scutellaria baicalensis., Conclusion: Different particle size of Scutellaria baicalensis leads to the differences of micromeritic properties. Superfine grinding III is determined as a better particle size.

There has been growing public concern regarding exposure to microwave fields as a potential human health hazard. This study aimed to identify sensitive biochemical indexes for the detection of injury induced by microwave exposure. Male Wistar rats were exposed to microwaves for 6 min per day, 5 days per week over a period of 1 month at an average power density of 5 mW/cm(2) (specific absorption rate of 2.1 W/kg). Urine specimens were collected over 24 h in metabolic cages at 7 days, 21 days, 2 months, and 6 months after exposure. (1)H NMR spectroscopy data were analyzed using multivariate statistical techniques. Urine metabolic profiles of rats after long-term microwave exposure were significantly differentiated from those of sham-treated controls using principal component analysis or partial least squares discriminant analysis. Significant differences in low molecular weight metabolites (acetate, succinate, citrate, ketoglutarate, glucose, taurine, phenylalanine, tyrosine, and hippurate) were identified in the 5 mW/cm(2) microwave exposure group compared with the sham-treated controls at 7 days, 21 days, and 2 months. Metabolites returned to normal levels by 6 months after exposure. These data indicated that these metabolites were related to the perturbations of energy metabolism particularly in the tricarboxylic acid cycle, and the metabolism of amino acids, monoamines, and choline in urine represent potential indexes for the detection of injury induced by long-term microwave exposure.

Objective: To analyze the effects of long-term microwave exposure on hippocampal structure and function in the rat., Methods: Experiments were performed on 184 male Wistar rats (three exposure groups and a sham group). Microwaves were applied daily for 6 min over 1 month at average power densities of 2.5, 5, and 10 mW/cm2. Learning and memory abilities were assessed by Morris water maze. High performance liquid chromatography was used to detect neurotransmitter concentrations in the hippocampus. Hippocampal structures were observed by histopathological analysis., Results: Following long-term microwave exposure there was a significant decrease in learning and memory activity in the 7 d, 14 d, and 1 m in all three microwave exposure groups. Neurotransmitter concentrations of four amino acids (glutamate, aspartic acid, glycine, and gamma-aminobutyric acid) in hippocampus were increased in the 2.5 and 5 mW/cm2 groups and decreased in the 10 mW/cm2 group. There was evidence of neuronal degeneration and enlarged perivascular spaces in the hippocampus in the microwave exposure groups. Further, mitochondria became swollen and cristae were disordered. The rough endoplasmic reticulum exhibited sacculated distension and there was a decrease in the quantity of synaptic vesicles., Conclusion: These data suggest that the hippocampus can be injured by long-term microwave exposure, which might result in impairment of cognitive function due to neurotransmitter disruption.

This work was aimed to investigate the effect of quinacrine on peripheral granulocytes and lymphocytes, interleukin 1 (IL-1) and interleukin 6 (IL-6) in peripheral blood serum of inflammatory reaction induced by microwave irradiation, and observe the protective effect of quinacrine against microwave irradiation injury. BALB/c mice were suffered from microwave irradiation with the total intensity of 50 mW/cm(2) for 30 minutes, at 1 hour before irradiation quinacrine (12.6 mg/kg or 50.4 mg/kg) was orally administrated. Mice received same volume of water for injection instead of quinacrine were named as microwave irradiation group (MR group), and mice received no microwave irradiation but stayed in microwave irradiation environment also for 30 min were set as control. After microwave irradiation, mice were sacrificed and peripheral blood cells were analyzed with cytoanalyzer, and mice serum interleukin-1β, interleukin-6 were detected by radioimmunoassay. The results showed that microwave irradiation increased the count of peripheral granulocytes and lymphocyte along with prolongation of time, while the increase of these cells in mice administrated quinacrine was markedly delayed. The level of IL-1β in serum of mice was significantly increased after 1 day of microwave irradiation (50 mW/cm(2)), and recovered to normal level after 7 days. The 2 concentrations of quinacrine (12.6 mg/kg, 50.4 mg/kg) could suppress level of IL-1β in serum induced by microwave irradiation. The level of IL-6 in serum of mice was gradually increased after microwave irradiation with intensity of 50 mW/cm(2) for 7 days, but quinacrine administration could delay the rise of IL-6 level, specially within time of 2 days. It is concluded that the quinacrine administration can delay the increase of peripheral granulocytes and lymphocytes inducted by microwave irradiation, and may partially suppress the rise of IL-1β and IL-6 in serum. The results of this study suggest that the quinacrine can provide some protective effect against microwave irradiation injury.

Objective: To investigate the effect of long-term microwave radiation on male reproduction in rats., Methods: A total of 100 male Wistar rats were exposed to microwave radiation with average power density of 0, 2.5, 5 and 10 mW/cm2 for 4 weeks, 5 times a week and 6 minutes per time. Changes in serum testosterone, testicular index, histology and ultrastructure, and the percentage of teratospermia in the epididymis were observed dynamically at 6 h, 7 d, 14 d, 28 d and 60 d after the exposure., Results: There was a significant decrease in serum testosterone concentration at 28 d after microwave radiation at 2.5, 5 and 10 mW/cm2 ([10.20 +/- 4.31] ng/ml, [5.56 +/- 3.47] ng/ml and [7.53 +/- 4.54] ng/ml) and at 60 d at 10 mW/cm2 ( [15.95 +/- 9.54] ng/ml), as compared with the control group ([23.35 +/- 8.06] ng/ml and [31.40 +/- 9.56] ng/ml) (P < 0.05 or P < 0.01). No significant changes were found in the testis index at 6 h -60 d after microwave radiation at the three doses, but different degrees of degeneration, necrosis and shedding of spermatogenic cells, thinning of spermatogenic epithelia, and decrease or deletion of spermatozoa were observed, and more obvious at 28 d and 60 d. Swelling and cavitation of mitochondria in all spermatogenic cells, agglutination and margin translocation of nuclear chromatin in the spermatogonial and Leydig cells were seen at 7 d and 60 d after 5 mW/cm2 microwave radiation. The rate of teratospermia of the epididymis was increased, more obviously at 7 d after 2.5, 5 mW/cm2, 60 d after 5 mW/cm2, and 7 d, 28 d and 60 d after 10 mW/cm2 microwave radiation (P < 0.05 or P < 0.01)., Conclusion: Long-term microwave radiation may cause injury to male reproduction, which is positively correlated with the radiation dose, and has an obvious late effect.

Objective: To explore the changes in the expressions of the tight junction related protein occludin and junctional adhesion molecule-1 (JAM-1) of the blood-testis barrier and their significance in rats after microwave radiation., Methods: Eighty male Wistar rats were exposed to microwave radiation with average power density of 0, 10, 30 and 100 mW/cm2 for five minutes, and dynamic changes in the expressions of testicular occludin and JAM-1 were observed by Western blot and image analysis at 6 h, 1 d, 3 d, 7 d and 14 d after the radiation., Results: There was a significant down-regulation in the expression of the occludin protein at 3 - 7 d, 6 h - 7 d and 6 h - 14 d (P < 0. 05), as well as in that of JAM-1 at 3 - 7 d, 1 - 7 d and 1-14 d (P < 0.05) after exposure to 10, 30 and 100 mW/cm2 microwave radiation., Conclusion: The decreased protein expressions of occludin and JAM-1 may play an important role in the microwave radiation induced-damage to the blood-testis barrier.

Objective: To investigate the expression of aquaporin 4 (AQP4) after microwave exposure and the correlation with the brain injury by radiation., Methods: 70 male rats were exposed to microwave whose average power density was 0, 10, 30 and 100 mW/cm(2) respectively. Rats were sacrificed at 6 h, 1 d, 3 d and 7 d after exposure. Immunohistochemistry and Western blot were used to detect the expression of AQP4 in protein level in rat hippocampus, and the expression of AQP4 in gene level was measured by in situ hybridization and RT-PCR., Results: The expression of AQP4 in rat hippocampus was abnormal after 10, 30, 100 mW/cm(2) microwave exposure. The protein level showed increased at first and then recovered at 10 and 30 mW/cm(2) groups, while increased progressively in 100 mW/cm(2) group within 14 d (P < 0.01). The gene expression of AQP4 was increased (0.51 +/- 0.02) at the beginning (6 h) and then regained after 10 mW/cm(2) microwave exposure, while in 30 and 100 mW/cm(2) groups, it rose to the peak at 7 d (0.46 +/- 0.02 and 0.43 +/- 0.08) and didn't get back (P = 0.004; P = 0.012)., Conclusion: Microwave radiation can increase the expression of AQP4 in rat hippocampus. The change might participate in the process of increasing permeability of blood-brain barrier and lead to the brain edema after microwave radiation.

To increase drug concentration in the head through intranasal administration, we have investigated the excised animal nasal mucosa permeability and nasal toxicity of the baicalin drug carrier systems, such as baicalin liposomes, beta-cyclodextrin inclusion compound, and phospholipid complex. A transport of baicalin drug carrier systems through nasal mucosa was simulated in diffusion chamber in vitro, and swine, caprine and rabbit nasal mucosa was used, the concentration of drug in the receptor was determined by HPLC. By taking the apparent permeability coefficients as evaluation standard, investigated the isolated animal nasal mucosa permeability of different baicalin drug systems was investigated for screening the best baicalin drug carrier system through nasal cavity administration. Toxicity of baicalin and its phospholipids complex on toad palate mucosal cilia movement and rats nasal mucosa long-term toxicity were studied in vivo. The apparent permeability coefficient of three kinds of baicalin drug carrier systems was better than that of baicalin (P < 0.05), and its lag-time was obviously shortened. At the same time, the apparent permeability coefficient of phospholipid complex was higher than those of other two drug carrier systems (P < 0.05). The results showed that the baicalin phospholipids complex nasal mucosa permeability was obviously superior to the other two drug systems. Baicalin phospholipids complex had no toxicity to ciliary movement, and had no irritation to rat nasal mucosa. The results show that baicalin phospholipid complex was the best baicalin drug carrier system, it could significantly enhance the permeability of baicalin across nasal mucosa, had no toxicity to nasal mucosa, and could be used for intranasal administration.

Aim: To investigate the effect of microwave radiation on expression and phosphorylation of synapsin I and to discover the mechanism by research on the change of expression of BDNF and its receptor, TrkB., Methods: PC12 cells were exposed to microwave with average power density being 30 mW/cm(2). HPLC was used to detect the release of amino acids; RT-PCR, Western blot and immunocytochemistry were used to detect the expressions of synapsin I, BDNF and TrkB; immune co-precipitation was used to study the interaction of BDNF and TrkB., Results: It resulted in the decrease of the release of Asp, Glu, GABA and Gly at 1 h (P<0.01) after radiation. Protein of synapsin I was decreased in 9 h-2 d (P<0.01 or P<0.05); its mRNA was decreased in 3-9 h and increased at 1 d (P<0.01 or P<0.05); its phosphorylation was decreased at 3 h, increased at 1 d, and decreased at 2 d again (P<0.01 or P<0.05) after radiation. Protein of BDNF was decreased at 3 h and increased in 1-2 d (P<0.01 or P<0.05); its mRNA were decreased in 3-9 h, increased at 1d, and decreased at 2 d again (P<0.01 or P<0.05) after radiation. Protein of TrkB was increased in 3 h-1 d (P<0.01 or P<0.05); its mRNA decreased at 3 h and 2 d (P<0.01) after radiation. The interaction between BDNF and TrkB was increased in 3-9 h, but decreased in 1-2 d (P<0.01 or P<0.05) after radiation., Conclusion: Microwave radiation can induce the decrease of the release of amino acids and the expression and phosphorylation of synapsin I, and the abnormality of expressions and interaction of BDNF and TrkB in PC12 cells. The factors might play a role in the injury and repair of information transmission in PC12 cells.

Objective: To investigate the effect of microwave radiation on synaptic structure, characteristic of synaptosome, the contents and release of neurotransmitters in hippocampus in Wistar rats., Methods: Wistar rats were exposed to microwave radiation with average power density of 30 mW/cm(2). Electron telescope was used to study the change of the synaptic structure at 6 h after radiation and to identify synaptosome. Flow cytometry and electron spin resonance were used to study the change of the concentration of Ca(2+) in synapse and the fluidity of membrane proteins of synaptosome. High performance liquid chromatography (HPLC) and spectrophotometer were used to study the changes of contents and release of amino acids and acetylcholine in hippocampus., Results: Microwave radiation of 30 mW/cm(2) caused deposits of synapse vesicle, elongation of active zone, the increase of thickness of postsynaptic density (PSD) and curvature, and perforation of synapse. The concentration of Ca(2+) in synapse (P<0.01) and tc of membrane proteins (P<0.01) of synaptosome increased contents of glutamic acid and glycine (P<0.01) and release of GABA increased the increase of contents and release of acetylcholine, and activity of acetyl cholinesterase (P<0.01) increased., Conclusion: Microwave radiation can induce the injure of synaptic structure and function of hippocampus, and then induce the disorder of the ability of learning and memory in rats.

Numerous studies have shown that acute microwave exposure causes cognitive deficits in animals, possibly via hyperthermia, but the biological effect of microwave exposure on memory processing is still unknown. The release of adenosine is demonstrated to be a general way for the cells to respond to metabolically stressful conditions such as hypoxia and ischemia. The present study aimed to examine whether adenosine mediates biological effects of microwave exposure on memory processing using a continuous multiple-trial inhibitory avoidance task. Results demonstrated that microwave exposure for 20 min before training impaired memory acquisition and retention performance in mice, assessed by the number of training trials and by latency to enter the dark compartment. The mice exposed to microwave radiation showed a dose-dependent hyperthermia. Moreover, the cell numbers of hippocampus were decreased in the mice receiving microwave exposure at an average power density of 50 mW/cm(2), indicating the anatomical correlation to hippocampal-amygdaloid structures corresponding with the memory disrupt of the mice. Administration of theophylline, a nonspecific adenosine receptor antagonist, 30 min before microwave exposure, completely antagonized the impairment of inhibitory avoidance acquisition but not retention. These results suggest that the adenosine regulation pathway was partially involved in microwave-induced impairment of inhibitory avoidance memory.

Objective: To evaluate the short and long-term outcomes between stenting with sirolimus eluting stent (SES) and spot stenting with small vessel stent (SVS) for treatment of small vessels with long lesions., Methods: 306 coronary heart disease patients in need of stenting in small vessel (diameter < 3.0 mm) with long lesions (> 20 mm) were divided into 2 groups: SES group (n = 93, receiving 157 CYPHER stents) and SVS group (n = 113, receiving spot stenting tactics). The clinical characteristics, success rate of procedure, rate of in-stent restenosis, target lesion revasculation (TLR), and major adverse cardiac events (MACE) were recorded after 6-month follow-up., Results: The baseline clinical and angiographic characteristics were similar between these two groups. Two CYPHER stents failed to pass the tortuous and calcified lesions in the SES group; DRIVER stents were used instead and succeeded in the passing. The rates of in-stent restenosis, TLR, and MACE of the SES group were 4.0%, 2.2%, and 3.2% respectively, all significantly, lower than those of the SVS group (26.5%, 10.6%, and 13.3% respectively, all P < 0.05)., Conclusion: In treatment of small vessel with long lesions, the rates of in-stent restenosis, TLR, and MACE are all much lower in the SES group than in the SVS group. Spot stenting with SVS may be feasible for small vessels with long and tortuous lesions, especially for those in which SES fails to pass through.

Objective: To explore the injury effect and mechanism of hypothalamic neurons after high power microwave (HPM) exposure., Methods: Primarily cultured hypothalamic neurons were exposed to 10 and 30 mW/cm(2) HPM, and the inverted phase contrast microscope (IPCM) and flow cytometry (FCM) were employed to detect the injury of cells and change of mitochondrion membrane potential (MMP) and Ca(2+) in the cytoplasm of neurons., Results: The ratio of apoptosis was significantly higher than that of the sham exposure (P < 0.05) induced by 10 and 30 mW/cm(2) HPM and necrosis increased significantly (P < 0.05) in the group of 30 mW/cm(2) at 6 h after exposure. The content of Ca(2+) in the cytoplasm of neuron cells increased (P < 0.01) while MMP decreased significantly (P < 0.01) after radiation of 30 mW/cm(2) HPM at 6 h after exposure., Conclusion: Apoptosis is one of the major death ways of hypothalamic neurons. The overloading of Ca(2+) and the decline of MMP are involved in the process.