Aim
Before the introduction of new biomaterials for prolapse surgery, animal studies on the host response are required. Unfortunately, large variation in study design hampers obtaining an overview of ...the safety and efficacy, and translation to clinical practice. Our aim is to systematically review the literature on all outcome measures describing the host response in animal studies assessing the biocompatibility of urogynecologic surgical mesh implants for prolapse surgery. Furthermore, by meta‐analysis, we aim to assess the effect of implantation and compare this to control animals receiving sham surgery or native tissue repair.
Methods
We performed a systematic search from inception to August 2020. Since this is an explorative study we included original, controlled, and noncontrolled animal studies describing any host response to the implant. Quantitative outcome measures reported ≥10 times in ≥2 articles were eligible for meta‐analysis.
Results
Fifty articles were included in the qualitative synthesis and 36 articles were eligible for meta‐analysis. In total, 154 outcome measures were defined and classified into (1) histomorphology, (2) biomechanics and, (3) macroscopic morphology. Animals with vaginal implants demonstrated significantly increased M1 and M2 macrophages, MMP‐2, neovascularization, TNF‐α, and stiffness, and lower vaginal contractility compared to control animals.
Conclusion
The host response significantly differs in animals after vaginal mesh implantation compared to control animals, both pro‐ and anti‐inflammatory. However, we observed a paucity in the uniformity of reported outcomes. For future animal studies, we propose the development of a core outcome set, which ideally predicts the host response in women.
The suboptimal outcomes of pelvic organ prolapse (POP) surgery illustrate the demand for improved therapies. However, their development is hampered by the limited knowledge on the cellular ...pathophysiology of POP. Current investigations, that are limited to tissues and 2D in vitro models, provide highly inconclusive results on how the extracellular matrix (ECM) metabolism and fibroblasts are affected in POP. This study uses a physiologically relevant 3D in vitro model to investigate the cellular pathophysiology of POP by determining the differences between POP and non‐POP fibroblasts on ECM metabolism, proliferation, and fibroblast‐to‐myofibroblast (FMT) transition. This model, based on the synthetic and biomimetic polyisocyanide hydrogel, enables the incorporation of mechanical loading, which simulates the forces exerted on the pelvic floor. Under static conditions, 3D cultured POP fibroblasts are less proliferative, undergo FMT, and exhibit lower collagen and elastin contents compared to non‐POP fibroblasts. However, under mechanical loading, the differences between POP and non‐POP fibroblasts are less pronounced. This study contributes to the development of more comprehensive models that can accurately mimic the POP pathophysiology, which will aid in an enhanced understanding and may contribute to improved therapies in the future.
The development of improved surgical therapies for pelvic organ prolapse (POP) is hampered by the limited knowledge on the cellular pathophysiology. Therefore, this study describes a physiologically relevant 3D in vitro model, to which mechanical loading can be applied, that allows to determine the differences between POP and non‐POP fibroblasts on extracellular matrix metabolism, proliferation, and fibroblast‐to‐myofibroblast transition.
There is an urgent need for improved outcomes in the treatment of pelvic organ prolapse (POP). Success of primary surgery relies on the load bearing capacity of plicated connective tissue underneath ...the vaginal wall, which is compromised due to an altered vaginal fibroblast function and collagen composition. There is an important factor in connective tissue repair that relates to changes in stiffness of the vaginal fibroblast microenvironment, which influences cell activity through cellular mechanosensing. The aim of this study is to investigate the effect of stiffness changes on vaginal fibroblast functions that relate to connective tissue healing in prolapse repair. The substrate stiffness was controlled by changing the polymer concentration in the fibrous and strongly biomimetic polyisocyanide (PIC) hydrogel. We analyzed stiffness during cell culture and assessed the consequential fibroblast proliferation, morphology, collagen deposition, and contraction. Our results show that increasing stiffness coincides with vaginal fibroblast alignment, promotes collagen deposition, and inhibits PIC gel contraction. These findings suggest that the matrix stiffness directly influences vaginal fibroblast functionality. Moreover, we observed a buildup in stiffness and collagen, with an enhanced fibroblast and collagen organization on the PIC-substrate, which indicate an enhanced structural integrity of the hydrogel-cell construct. An improved tissue structure during healing is relevant in the functional repair of POP. Therefore, this study encourages future research in the use of PIC gels as a supplement in prolapse surgery, whereby the hydrogel stiffness should be considered.
The high reoperation rate in pelvic organ prolapse (POP) surgery is probably due to impaired wound healing, and therefore, novel strategies that promote tissue regeneration are urgently needed. ...Estrogen therapy shows beneficial effects for vaginal wound healing: it reduces the inflammatory response and improves vaginal tissue strength and quality. Earlier, scaffolds that release the most potent estrogen, β‐estradiol (E2) have been described. This work describes the results of conjugating E2 covalently to the synthetic, but highly mimetic, polyisocyanide hydrogel (PIC‐E2). As adipose‐derived stem cells (ASCs) possess regenerative capabilities, the combination of PIC‐E2 and ASCs may have a synergistic effect on pelvic floor tissue regeneration. The results show that the PIC‐E2 bioactivity is not hampered upon covalent E2 conjugation and upregulates various extracellular matrix (ECM) genes in ASCs. Moreover, PIC‐E2 exerts similar effects regarding ECM metabolism compared to other E2‐releasing biomaterials, but at much lower doses, which is economically and therapeutically favorable. Based on these in vitro findings, the combination of the PIC‐E2 hydrogel and ASCs may have the potential to stimulate tissue regeneration in vivo, and therefore, feasibly improve the surgical outcomes for POP in the future.
β‐Estradiol has the potential to stimulate pelvic floor tissue regeneration. Its covalent conjugation to the polyisocyanide‐based hydrogel does not hamper its bioactivity and upregulates extracellular matrix genes in adipose‐derived stem cells. The results suggest that the combination of the hormone‐modified gel with the stem cells holds the potential to stimulate regeneration of the pelvic floor tissues.
Three patients suffering from a treatment-resistant depression were being treated with a monoamine oxidase (mao-)inhibitor and received lithium augmentation to achieve better recovery. One patient ...showed significant improvement of depressive symptoms within 24 hours, one patient showed very little respons and one patient did not respond at all. Literature research led to other casereports, where adding lithium to mao-inhibitors had also been effective. The growing amount of arguments of a positive effect of lithium augmentation to mao-inhibitors asks for more research to collect more evidence and a better understanding of this new, potentially effective treatment.
A Young Dancer Survey Kish, Robin L; Plastino, Janice Gudde; Martyn-Stevens, Bethany
Medical problems of performing artists,
12/2003, Letnik:
18, Številka:
4
Journal Article
Recenzirano
The purpose of this study was to determine, through self-reporting techniques, the training and injury rates among students studying dance in the private sector. The private studio provides the major ...venue for students to study dance. This is especially true for young students (ages
8-18) who study ballet, jazz, and tap and who participate in dance competitions. A private dance studio is defined as a studio open to the community with no audition requirements for entry that teaches various technique styles. Private studio dancers are not training specifically to
be professional dancers in major ballet companies. Few data exist regarding the training or injury rates of these students in part because of difficulties with access and compliance. To date, 3,700 surveys have been distributed (January 2001-present) to students training in private studios
throughout California. Information was requested concerning current and past injuries, dance training history, and competition schedules. This ongoing investigation currently has examined 173 (male = 6 and female = 167) completed surveys. The mean age of dancers who responded to the survey
was 15.2 years. Of the dancers surveyed, 93% study at private dance studios, and 67% have studied in high school dance programs. The number of injuries reported (n = 226) included fractures, strains, sprains, and tendinitis. The ankle, knee, and back were found to be the most frequent injury
sites. Correlations between the number of different techniques studied and the total hours danced, the number of different techniques studied and number of injuries for each individual, and the number of injuries for each individual and total hours danced all were significant at 0.01. Initial
results support that dancers in the private dance studio are susceptible to injuries similar to those experienced by dancers in elite training centers.
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