Technologic innovations, expensive new therapies, and improved access to treatment have all contributed to the rising costs of oncologic care in the United States. 1 The financial consequences for patients and their families are substantial. Patients with cancer often borrow money, avoid leisure activities, decrease food spending, sell possessions, go into debt, and/or declare bankruptcy, 2 and they are at greater risk for disability or unemployment. 3 These consequences are particularly great for patients who are underinsured or uninsured. Recently, online crowdfunding platforms are being increasingly used to supplement insurance and defray expenses, even for experimental and unproven treatments. 4 We sought to characterize the use of crowdfunding to support oncology care needs, including any association between insurance status and other characteristics.
The urethra within the human penile shaft develops via (1) an "Opening Zipper" that facilitates distal canalization of the solid urethral plate to form a wide urethral groove and (2) a "Closing Zipper" that facilitates fusion of the epithelial surfaces of the urethral folds. Herein, we extend our knowledge by describing formation of the human urethra within the glans penis as well as development of the prepuce. Forty-eight normal human fetal penile specimens were examined using scanning electron microscopy and optical projection tomography. Serial histologic sections were evaluated for morphology and immunohistochemical localization for epithelial differentiation markers: Cytokeratins 6, 7, 10, FoxA1, uroplakin and the androgen receptor. As the closing zipper completes fusion of the urethral folds within the penile shaft to form a tubular urethra (~ 13 weeks), canalization of the urethral plate continues in proximal to distal fashion into the glans penis to directly form the urethra within the glans without forming an open urethral groove. Initially, the urethral plate is attached ventrally to the epidermis via an epithelial seam, which is remodeled and eliminated, thus establishing mesenchymal confluence ventral to the glanular urethra. The morphogenetic remodeling involves the strategic expression of cytokeratin 7, FoxA1 and uroplakin in endodermal epithelial cells as the tubular glanular urethra forms. The most ventral epithelial cells of the urethral plate are pinched off from the glanular urethra and are reabsorbed into the epidermis ultimately losing expression of their markers, a process undoubtedly regulated by androgens. The prepuce initially forms on the dorsal aspect of the glans at approximately 12 weeks of gestation. After sequential proximal to distal remodeling of the ventral urethral plate along the ventral aspect of glans, the prepuce of epidermal origin fuses in the ventral midline.
Purpose Complementary and alternative medicine (CAM) use is common amongst cancer patients. However, there is growing concern about its safety and efficacy. Online crowdfunding campaigns represent a unique avenue to understand the cancer patient's perspective for using CAM or declining conventional cancer therapy (CCT). Methods Five hundred GoFundMe campaigns from 2012 to 2019 detailing financial need for cancer treatment were randomly selected and reviewed for endorsement of CAM use, reasons for using CAM, and reasons for declining CCT. Descriptive statistics were used to compare patient and campaign characteristics between 250 CAM users and 250 non-CAM users. Results Compared to non-CAM users, CAM users were more likely to be female (70% vs. 54%, p < 0.01), to report more stage IV cancer (54% vs. 12%, p < 0.01), and to have a history of delayed, missed, or misdiagnosis (10% vs. 4%, p < 0.01). Reasons for using CAM include endorsing curative/therapeutic effects 212 (85%), pain/stress reduction 137 (55%), and dissatisfaction with current or past medical treatment options 105 (42%). 87 (35%) CAM users that declined CCT reported that they wanted to try to fight off cancer using CAM first 57 (61%), that CCT was too "toxic" to the body 39 (42%), and cancer was already too advanced, so that CCT would be futile or too aggressive 25 (27%). Conclusion Cancer patients on GoFundMe using CAM highly value quality of life, comfort, and autonomy. Physicians should educate themselves on CAM to set realistic expectations and provide comprehensive counseling of the risks and benefits of CAM usage to patients who choose to use CAM to either augment or completely replace CCT.
The urinary bladder collects urine from the kidneys and stores it until the appropriate moment for voiding. The trigone and ureterovesical junctions are key to bladder function, by allowing one-way passage of urine into the bladder without obstruction. Embryological development of these structures has been studied in multiple animal models as well as humans. In this report we review the existing literature on bladder development and cellular signalling with particular focus on bladder development in humans. The bladder and ureterovesical junction form primarily during the fourth to eighth weeks of gestation, and arise from the primitive urogenital sinus following subdivision of the cloaca. The bladder develops through mesenchymal-epithelial interactions between the endoderm of the urogenital sinus and mesodermal mesenchyme. Key signalling factors in bladder development include shh, TGF-β, Bmp4, and Fgfr2. A concentration gradient of shh is particularly important in development of bladder musculature, which is vital to bladder function. The ureterovesical junction forms from the interaction between the Wolffian duct and the bladder. The ureteric bud arises from the Wolffian duct and is incorporated into the developing bladder at the trigone. It was previously thought that the trigonal musculature developed primarily from the Wolffian duct, but it has been shown to develop primarily from bladder mesenchyme. Following emergence of the ureters from the Wolffian ducts, extensive epithelial remodelling brings the ureters to their final trigonal positions via vitamin A-induced apoptosis. Perturbation of this process is implicated in clinical obstruction or urine reflux. Congenital malformations include ureteric duplication and bladder exstrophy.
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