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Rodney L Dunn

Publications and source records attributed to Rodney L Dunn.

71 records · Page 4Linked to original sources

The impact of co-morbid disease on cancer control and survival following radical cystectomy.

PURPOSE: We clarified the impact of concurrent medical disease on tumor control and survival following radical cystectomy. MATERIALS AND METHODS: A total of 106 consecutive patients with clinically localized (cT2 or less) disease underwent radical cystectomy at the University of Michigan between 1997 and 1998. The Charlson Index, a validated risk adjustment index, was used to assess preoperative co-morbidity. The 3 primary end points were pathological stage, disease specific survival and overall survival. Logistic regression models were used to determine the relationship between Charlson Index and pathological stage, while Cox regression models were used for the 2 survival end points. RESULTS: Of our study population 24% had a Charlson Index score of 2 or greater. Myocardial infarction, nonurothelial solid malignancies and cerebrovascular disease were the most common co-morbid conditions at 14%, 12% and 10%, respectively. On bivariate analysis the Charlson Index was significantly associated with decreased disease specific (p = 0.049) and overall (p = 0.016) survival. In a multivariate model the index was independently associated with decreased cancer specific survival (p = 0.049) and increased risk of extravesical disease (p = 0.033). CONCLUSIONS: We demonstrated an association between co-morbid illness and adverse pathological and survival outcome following radical cystectomy. This finding underscores the value of assessing overall health before recommending and proceeding with surgery. Moreover, our results emphasize the need to adjust for co-morbidity when comparing outcomes following radical cystectomy.

Aged↗

Comparison of lower urinary tract symptom severity and associated bother between community-dwelling black and white men: the Olmsted County Study of Urinary Symptoms and Health Status and the Flint Men's Health Study.

OBJECTIVES: To determine the magnitude of racial disparity in lower urinary tract symptom (LUTS) severity and bother by combining two large comparable epidemiologic studies of community-dwelling white and black men, thereby avoiding many of the referral biases present in previous studies. Prior studies evaluating racial differences in benign prostatic hyperplasia have been hampered by selection bias, because nearly all have used surgical treatment as a marker for benign prostatic hyperplasia. METHODS: Data from the Olmsted County Study of Urinary Symptoms and Health Status and the Flint Men's Health Study were combined for a total study sample of 2480 men. We examined LUTS severity and associated bother as measured by the self-administered American Urological Association Symptom Index and Symptom Problem Index. RESULTS: Overall 34% of white men reported moderate/severe LUTS compared with 41% of black men (P <0.001). These patterns were consistent across age and persisted after adjustment for age and other sociodemographic factors. The relationship between LUTS severity and bother differed by race in that black men reported less bother for each unit increase in LUTS (P <0.001). CONCLUSIONS: In contrast to studies based on clinical populations, our community-based study demonstrated greater LUTS severity in black men compared with white men but black men reported less bother for any given level of LUTS severity. Although these findings suggest a racial disparity in benign prostatic hyperplasia, additional studies of anatomic, physiologic, and molecular factors may clarify whether these racial differences are real or due to sociocultural differences in reporting symptom morbidity.

Adult↗

Ultra-rapid freezing of very low numbers of sperm using cryoloops.

BACKGROUND: With the availability of ICSI, men with severe oligozoospermia (<5x10(6)/ml) are able to reproduce. Current methods for cryopreservation of severe oligozoospermic samples are labour intensive and costly. The objective of this study was to evaluate whether freezing small numbers of motile sperm (approximately 100) was feasible using cryoloops. METHODS: Initial tests assessed the effect of various dilutions of cryoprotectants on pre-freezing sperm motility. Several solutions were further evaluated for their ability to cryoprotect sperm during ultra-rapid freezing. Sperm were placed on cryoloops and held in liquid nitrogen vapour for 5 min prior to freezing (ultra-rapid freezing) or directly submerged into liquid nitrogen. Using the optimal cryoprotectant and technique from these experiments, ultra-rapid and standard slow-rate freezing protocols were compared. RESULTS: Optimal sperm survival was seen when sperm in cryoloops were placed in liquid nitrogen vapour in test yolk buffer with 12% v/v glycerol versus other cryoprotectants. Using this cryoprotectant, post-thaw sperm motility is comparable between ultra-rapid and slow-rate freezing methods. CONCLUSION: Ultra-rapid freezing of very low numbers of sperm is feasible using cryoloops suspended in liquid nitrogen vapour for 5 min.

Cell Survival↗

Determinants of long-term sexual health outcome after radical prostatectomy measured by a validated instrument.

PURPOSE: We combined the strengths of previous patient reported studies (that is use of a validated instrument) with the assets of previous single surgeon, physician reported series (that is prospective collection of operative data) by performing a multiple surgeon study to identify demographic and operative determinants of post-prostatectomy sexual health related quality of life outcomes. MATERIALS AND METHODS: Sexual outcome was measured after prostatectomy in 671 prostate cancer cases with a followup of 4 to 52 months treated by any of 7 urologists at a high volume medical center and 112 age matched controls by cross-sectional health related quality of life assessment using the Expanded Prostate Cancer Index Composite validated questionnaire. Multivariable ANCOVA was done to identify the baseline determinants affecting post-prostatectomy sexual health outcomes among 17 clinical and demographic factors. RESULTS: Factors independently associated with better sexual health outcome in patients included younger age (p <0.0001), nerve sparing technique (p <0.0001), time since prostatectomy (p = 0.0001), smaller prostate size (p = 0.003), higher education level (p = 0.02), and higher household income (p = 0.02). Orgasm was achieved at a higher rate than erection. In controls only age (p = 0.0004) and having a partner (p = 0.04) were significantly associated with sexual health. CONCLUSIONS: Larger prostate size adversely affected sexual health outcome after radical prostatectomy independent of all other measured factors. Patient sexual outcome did not differ significantly among surgeons who performed a broad range of such procedures yearly, suggesting that surgical expertise cannot be measured simply by the number of such operations that a surgeon performs. Stratifying patient reported sexual function by the principal determinants of age, nerve sparing and prostate size provides a basis for counseling patients.

Aged↗

Hautmann and Studer orthotopic neobladders: a contemporary experience.

PURPOSE: The development of Studer and Hautmann orthotopic neobladders has revolutionized the management of urinary diversion. Several series have promoted 1 technique over the other. We examine the clinical outcome of a contemporary cohort of patients with bladder cancer who underwent either Hautmann or Studer orthotopic reconstruction. MATERIALS AND METHODS: Retrospective analysis was performed on 130 patients who underwent cystectomy and orthotopic diversion (Studer 93 and Hautmann 37) between March 1, 1995 and September 30, 2000. Clinical parameters evaluated were age, gender, procedure time, length of hospital stay, blood loss, pathological stage, and rates of complication, continence and reoperation. Diversion type was compared with clinical parameters using Fisher's exact test, t-test and Wilcoxon rank sum analysis. RESULTS: Studer and Hautmann techniques had mean procedure times of 5.9 and 5.3 hours, respectively (p = 0.003), and mean length of stay was shorter for Hautmann than Studer (7.0 versus 8.3 days, respectively, p = 0.02). When comparing both populations there was no difference in age, gender, estimated blood loss, pathological stage or rates of complication and reoperation. Total continence was similar in the Hautmann and Studer cohorts, whether during the day (67% versus 67%) or at night (47% versus 40%), respectively. CONCLUSIONS: The data suggest that both orthotopic techniques can be performed in men and women in a safe and timely fashion. Nighttime continence rates are slightly higher with the Hautmann technique, although not statistically different. The shortened Hautmann procedure time likely relates to variations in the ureteral anastomosis. Decreased length of stay may reflect recent trends of early hospital discharge.

Female↗

Phase II trial of tetrathiomolybdate in patients with advanced kidney cancer.

PURPOSE: Tetrathiomolybdate (TM), a copper-lowering agent, has been shown in preclinical murine tumor models to be antiangiogenic. We evaluated the antitumor activity of TM in patients with advanced kidney cancer in a Phase II trial. EXPERIMENTAL DESIGN: Fifteen patients with advanced kidney cancer were eligible to participate in this trial. TM was initiated p.o. at 40 mg three times a day with meals and 60 mg at bedtime to deplete copper. A target serum ceruloplasmin (CP) level of 5-15 mg/dl was defined as copper depletion. Doses of TM were reduced for grade 3-4 toxicity and to maintain a CP level in the target range. Once copper depletion was attained, patients underwent baseline tumor measurements and then again every 12 weeks for response assessment. Patients not exhibiting progressive disease at 12 weeks after copper depletion continued on treatment. Serum levels of Interleukin (IL)-6, IL-8, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were assayed pretreatment and at various time points on treatment. Dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI) was performed on selected patients in an attempt to assess changes in tumor vascularity. RESULTS: All of the patients rapidly became copper depleted. Thirteen patients were evaluable for response. No patient had a complete response or PR. Four patients (31%) had stable disease for at least 6 months during copper depletion (median, 34.5 weeks). TM was well tolerated, with dose reductions most commonly occurring for grade 3-4 granulocytopenia of short duration not associated with febrile episodes. Serum levels of IL-6, IL-8, VEGF, and bFGF did not correlate with clinical activity. Serial DCE-MRI was performed only in four patients, and a decrease in vascularity seemed to correlate with necrosis of a tumor mass associated with tumor growth. CONCLUSIONS: TM is well tolerated and consistently depletes copper as measured by the serum CP level. Clinical activity was limited to stable disease for a median of 34.5 weeks in this Phase II trial in patients with advanced kidney cancer. Serum levels of proangiogenic factors IL-6, IL-8, VEGF, and bFGF may correlate with copper depletion but not with disease stability in this small cohort. TM may have a role in the treatment of kidney cancer in combination with other antiangiogenic therapies.

Aged↗

Relationship of serum sex-steroid hormones and prostate volume in African American men.

BACKGROUND: Previous epidemiologic investigations of the associations of sex-steroid hormones and benign prostatic hyperplasia (BPH) have focused on predominately white populations. The objective of this study was to evaluate potential associations of body mass index (BMI), cigarette smoking, use of alcohol, and endogenous sex-steroid hormones with prostate volume in a population-based sample of African American (AA) men, ages 40-79 yr. METHODS: A total of 369 AA men without clinical evidence of prostate cancer were identified in the Flint Men's Health Study by using a population-based sampling procedure. All subjects underwent a complete urologic evaluation that included prostate volume determination by transrectal ultrasonography and serum assays for androgens and estrogens. RESULTS: After age adjustment, BMI (weight (kg)/height (m)2) was positively correlated with increasing levels of androstanediol glucuronide (AG), estradiol (E2), estrone sulfate (E1S), and the ratios of E2:total testosterone (TT) and E2:free testosterone (FT); however, increasing BMI was negatively correlated with androstenedione (AD), FT, TT, and sex hormone-binding globulin (SHBG). Multivariable regression models demonstrated that prostate volume increased with age (P < 0.001) and BMI (P = 0.02) and decreased with increasing levels of SHBG (P = 0.01). Larger prostatic volumes were also marginally associated with increasing levels of TT (P = 0.058). CONCLUSION: Circulating serum levels of SHBG and endogenous sex-steroid hormones are correlated with prostate volume and potentially impact the natural history of BPH. However, longitudinal studies are needed to demonstrate the temporal relationships of hormones and growth factors in the pathogenesis of BPH in AA men.

Adult↗

Comprehensive comparison of health-related quality of life after contemporary therapies for localized prostate cancer.

PURPOSE: Health-related quality-of-life (HRQOL) concerns are pivotal in choosing prostate cancer therapy. However, concurrent HRQOL comparison between brachytherapy, external radiation, radical prostatectomy, and controls is hitherto lacking. HRQOL effects of hormonal adjuvants and of cancer control after therapy also lack prior characterization. PATIENTS AND METHODS: A cross-sectional survey was administered to patients who underwent brachytherapy, external-beam radiation, or radical prostatectomy during 4 years at an academic medical center and to age-matched controls. HRQOL among controls was compared with therapy groups. Comparison between therapy groups was performed using regression models to control covariates. HRQOL effects of cancer progression were evaluated. RESULTS: One thousand fourteen subjects participated. Compared with controls, each therapy group reported bothersome sexual dysfunction; radical prostatectomy was associated with adverse urinary HRQOL; external-beam radiation was associated with adverse bowel HRQOL; and brachytherapy was associated with adverse urinary, bowel, and sexual HRQOL (P < or =.0002 for each). Hormonal adjuvant symptoms were associated with significant impairment (P <.002). More than 1 year after therapy, several HRQOL outcomes were less favorable among subjects after brachytherapy than after external radiation or radical prostatectomy. Progression-free subjects reported better sexual and hormonal HRQOL than subjects with increasing prostate-specific antigen (P <.0001). CONCLUSION: Long-term HRQOL after prostate brachytherapy showed no benefit relative to radical prostatectomy or external-beam radiation and may be less favorable in some domains. Hormonal adjuvants can be associated with significant impairment. Progression-free survival is associated with HRQOL benefits. These findings facilitate patient counseling regarding HRQOL expectations and highlight the need for prospective studies sensitive to urinary irritative and hormonal concerns in addition to incontinence, sexual, and bowel HRQOL domains.

Aged↗

Conventional diamond fraise vs manual spot dermabrasion with drywall sanding screen for scars from skin cancer surgery.

OBJECTIVE: To directly compare cosmetic improvement and postoperative sequelae resulting from dermabrasion of surgical scars with conventional motor-powered diamond fraise vs manual dermabrasion with medium-grade drywall sanding screen. DESIGN: Patients were randomly assigned to receive treatment with conventional diamond fraise dermabrasion to one half of the scar and manual dermabrasion with a drywall sanding screen to the other half in a prospective, comparative clinical study. Blinded observers assessed clinical variables during a 6-month follow-up period. SETTING: University hospital/cancer center-based cutaneous surgery unit. PATIENTS: Twenty-one healthy volunteers, Fitzpatrick skin type I to III, with contour irregularities resulting from granulation (7 patients) or reconstruction (14 patients) after skin cancer excision. INTERVENTIONS: One half of the patient's scar was treated with motor-powered diamond fraise dermabrasion and the other half was treated with manual dermabrasion with medium-grade drywall sanding screen. MAIN OUTCOME MEASURES: Correction of contour, scarline visibility, time to reepithelialization, presence or absence of milia, degree of postoperative erythema, hypertrophic scarring, patients' subjective reports of postoperative pain, and presence of pigmentary changes were observed for both methods. Standardized scoring systems were used to quantify outcome measures. RESULTS: According to the standardized scoring systems, no differences were found between the 2 methods at any point. In addition, no significant differences were found between the methods for any measure at any of the time points. CONCLUSION: Both dermabrasion techniques are equally effective in improving the cosmetic appearance of surgical scars.

Adult↗

alpha-Methylacyl-CoA racemase: expression levels of this novel cancer biomarker depend on tumor differentiation.

alpha-Methylacyl-CoA racemase (AMACR) has previously been shown to be a highly sensitive marker for colorectal and clinically localized prostate cancer (PCa). However, AMACR expression was down-regulated at the transcript and protein level in hormone-refractory metastatic PCa, suggesting a hormone-dependent expression of AMACR. To further explore the hypothesis that AMACR is hormone regulated and plays a role in PCa progression AMACR protein expression was characterized in a broad range of PCa samples treated with variable amounts and lengths of exogenous anti-androgens. Analysis included standard slides and high-density tissue microarrays. AMACR protein expression was significantly increased in localized hormone-naive PCa as compared to benign (P < 0.001). Mean AMACR expression was lower in tissue samples from patients who had received neoadjuvant hormone treatment but still higher compared to hormone-refractory metastases. The hormone-sensitive tumor cell line, LNCaP, demonstrated stronger AMACR expression by Western blot analysis than the poorly differentiated cell lines DU-145 and PC-3. AMACR protein expression in cells after exposure to anti-androgen treatment was unchanged, whereas prostate-specific antigen, known to be androgen-regulated, demonstrated decreased protein expression. Surprisingly, this data suggests that AMACR expression is not regulated by androgens. Examination of colorectal cancer, which is not hormone regulated, demonstrated high levels of AMACR expression in well to moderately differentiated tumors and weak expression in anaplastic colorectal cancers. Taken together, these data suggest that AMACR expression is not hormone-dependent but may in fact be a marker of tumor differentiation.

Biomarkers, Tumor↗

Neoadjuvant hormonal therapy and older age are associated with adverse sexual health-related quality-of-life outcome after prostate brachytherapy.

OBJECTIVES: Brachytherapy is increasingly used as a treatment for localized prostate cancer but information regarding long-term, postimplantation, patient-reported sexual health-related quality-of-life (HRQOL) is scant. Neoadjuvant hormonal therapy is commonly administered with brachytherapy, yet its potentially adverse effects on subsequent sexual health have not been described using a validated HRQOL instrument. We used a validated HRQOL survey to characterize the significance of neoadjuvant hormonal therapy and other baseline factors on postimplantation sexual function and impairment. METHODS: A cross-sectional survey using the expanded prostate cancer index composite HRQOL instrument was administered to all 114 localized prostate cancer patients who underwent ultrasound-guided, transperineal brachytherapy during a 4-year period and to 142 age-matched control men. Multivariable models measured the association of baseline factors and covariates with postimplantation sexual HRQOL. RESULTS: Older age (P = 0.01) and neoadjuvant hormonal therapy (P = 0.009) were independently associated with diminished sexual HRQOL after prostate brachytherapy. Among patients younger than 69 years old, 33% reported at least fair sexual function after brachytherapy alone compared with 19% of men after brachytherapy with neoadjuvant hormonal therapy. Of the age-matched control men younger than 69 years old, 78% reported at least fair sexual function. Among patients older than 69 years, 26% reported at least fair sexual function after brachytherapy alone compared with 5% after brachytherapy with neoadjuvant hormonal therapy, and 61% of age-matched controls reported at least fair sexual function. CONCLUSIONS: Patient age and neoadjuvant hormonal therapy are independent, significant determinants of sexual HRQOL after prostate brachytherapy. These factors should be taken into consideration when counseling patients with localized prostate cancer regarding the expected, postimplantation sexual HRQOL outcome.

Age Factors↗

Regulation of spindle formation by active mitogen-activated protein kinase and protein phosphatase 2A during mouse oocyte meiosis.

Mitogen-activated protein kinase (MAPK) and protein phosphatase 2A (PP2A) regulate oocyte meiosis, yet little is known regarding their mechanisms of action. This study addressed the functional importance of active MAPK and PP2A in regulating oocyte meiosis. Experiments were conducted to identify MAPK activation, PP2A activity, intracellular enzyme trafficking, and ultrastructural associations during meiosis. Questions of requisite kinase and/or phosphatase activity and chromatin condensation, microtubule polymerization, and spindle formation were addressed. At the protein level, MAPK and PP2A were present in constant amounts throughout the first meiotic division. Both MAPK and PP2A were activated following germinal vesicle breakdown (GVBD) in conjunction with metaphase I development. Immunocytochemical studies confirmed the absence of active MAPK in germinal vesicle-intact (GVI) and GVBD oocytes. At metaphase I and during the metaphase I/metaphase II transition, activated MAPK colocalized with microtubules, poles, and plates of meiotic spindles. Protein phosphatase 2A was dispersed evenly throughout the GVI oocyte cytoplasm. Throughout the metaphase I/metaphase II transition, PP2A colocalized with microtubules of meiotic spindles. Both active MAPK and PP2A associated with in vitro-polymerized microtubules, suggesting that active MAPK and PP2A locally regulate spindle formation. Inhibition of MAPK activation resulted in compromised microtubule polymerization, no spindle formation, and loosely condensed chromosomes. Treatment with okadaic acid (OA) or calyculin-A (CL-A), which inhibits oocyte cytoplasmic PP2A, caused an absence of microtubule polymerization and spindles, even though MAPK activity was increased under these treatment conditions. Thus, active MAPK is required, but is not sufficient, for normal meiotic spindle formation and chromosome condensation. In addition, the oocyte OA/CL-A-sensitive PP, presumably PP2A, is essential for microtubule polymerization and meiotic spindle formation.

Animals↗

Getting patients to the right healthcare sources: from real-world questions to strategy hubs.

To address the growing problem of novices accessing incomplete and unreliable information on the Web, this paper begins by probing the nature of strategic knowledge known by expert healthcare searchers. The analysis reveals the existence of a strategy that is focused to a specific type of healthcare question. To investigate whether there exist other similar strategies, we conduct two pilot studies. The first leads to the development of a taxonomy for skin cancer questions based on real-world questions. This taxonomy has high inter-rater agreement when tested with new real-world questions. The second pilot helps to identify 6 strategies that are specific to question types in the taxonomy. We demonstrate how these strategies can be made available to a wide range of users through a prototypical system referred to as a Strategy Portal. In conclusion, we briefly describe our current and future research to test if such a system can make patients more effective and efficient in the retrieval of reliable and relevant healthcare information on the Web.

Delivery of Health Care↗

The effects of stage divergence on survival after radical cystectomy for urothelial cancer.

INTRODUCTION: Discrepancies between clinical and pathologic staging, herein referred to as stage divergence, are common after radical cystectomy. The implications of stage divergence on survival are ill defined in the context of those treated by surgery alone and would facilitate patient counseling and enhance prognostication. METHODS: There were 78 consecutive radical cystectomy patients with clinical stage T2 or less urothelial carcinoma who comprised our study population. Kaplan-Meier plots were constructed to determine the effects of stage divergence on survival and the log-rank test employed to assess the significance. Regression models were developed to determine predictors of overall and cancer-specific survival. RESULTS: Stage divergence was common after radical cystectomy with downstaging and upstaging occurring in 27% and 49% of patients, respectively. Downstaged patients had better overall (P = 0.003) and bladder cancer-specific (P = 0.0004) survivals. None of the downstaged patient died from bladder cancer (median follow-up 35.9 months). Upstaged patients were five times as likely to succumb from bladder cancer or other illness compared to downstaged patients. This effect was not isolated to patients with lower clinical stages but also demonstrated in patients with clinical stage T2 bladder cancer. CONCLUSIONS: Stage divergence is common after radical cystectomy occurring in 76% of patients in this study. The implications of stage divergence are equally relevant for those who are upstaged or downstaged in terms of survival, and such data is useful when counseling patients postoperatively. Downstaging at the time of radical cystectomy is associated with better overall and cancer-specific survival.

Aged↗

Contemporary preoperative parameters predict cancer-free survival after radical prostatectomy: a tool to facilitate treatment decisions.

Prostate specific antigen (PSA) screening has heralded stage migration in prostate cancer toward cancers that may be readily eliminated by primary intervention. We sought to identify contemporary, preprostatectomy measures of cancer severity useful and significant for predicting postprostatectomy, recurrence-free survival. The association of baseline variables clinical variables (age, clinical stage, serum PSA, and race) and prostate biopsy parameters (Gleason score, presence of perineural invasion, number of biopsy cores with cancer, and the greatest percentage of a biopsy core occupied by cancer--GPC) with recurrence-free survival was evaluated by multivariate Cox proportional hazards regression among consecutive patients that underwent radical prostatectomy as primary therapy between 1994 and 2002. Tables were generated depicting expected 5-year recurrence-free survival after prostatectomy. From 1414 patients, 183 developed biochemical recurrence, 8 died from prostate cancer, and 31 died of all causes. Multivariable Cox regression found that clinical stage, PSA, Gleason score, and the greatest percentage of a biopsy core involved by cancer (GPC), were each significant determinants of post-prostatectomy, PSA recurrence-free survival (P < 0.05 for each). Gleason score and GPC were also significantly associated with clinical recurrence-free survival and cancer death, whereas other biopsy parameters and PSA were not. The amount of cancer in a biopsy core is a significant predictor of recurrence-free survival after prostatectomy, and is a simple clinical measure that complements baseline PSA, and Gleason score in predicting outcome. Tabulated 5-year PSA-free survival outcomes, stratified by these preoperative parameters, provide a basis for preoperative counseling of patients regarding postprostatectomy cancer control expectations.

Adenocarcinoma↗

In vivo visualization of metastatic prostate cancer and quantitation of disease progression in immunocompromised mice.

While survival periods for patients with localized prostate cancer have increased, there is still no curative therapy for metastatic disease. Using non-invasive bioluminescent imaging, we designed a comprehensive murine model to monitor tumor location and expansion. We detected micrometastases after one week that correlated by gross necropsy, autoradiography, and histopathology with organ and skeletal lesions seen clinically. We calculated in vivo kinetics for tumor growth based on biophoton emissions and observed significantly faster growth of bone lesions and of overall tumor burden in young mice compared to old mice. This model provides a controllable biological system for further investigation into the pathogenesis of metastatic prostate cancer and evaluation of new therapies.

Animals↗