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Pelvic organ prolapse (POP) is a benign disease characterized by the descent of pelvic organs due to weakened pelvic floor muscles and fascial tissues. Primarily affecting elderly women, POP can lead to various urinary and gastrointestinal tract symptoms, significantly impacting their quality of life. The pathogenesis of POP predominantly involves nerve–muscle damage and disorders in the extracellular matrix metabolism within the pelvic floor. Recent studies have indicated that genetic factors may play a crucial role in this condition. Focusing on linkage analyses, single-nucleotide polymorphisms, genome-wide association studies, and whole exome sequencing studies, this review consolidates current research on the genetic predisposition to POP. Advances in epigenetics are also summarized and highlighted, aiming to provide theoretical recommendations for risk assessments, diagnoses, and the personalized treatment for patients with POP. [ABSTRACT FROM AUTHOR]

For more than 40 years, autologous platelet concentrates have been used in clinical medicine. Since the first formula used, namely platelet-rich plasma (PRP), other platelet concentrates have been experimented with, including platelet-rich fibrin and concentrated growth factor. Platelet concentrates have three standard characteristics: they act as scaffolds, they serve as a source of growth factors and cytokines, and they contain live cells. PRP has become extensively used in regenerative medicine for the successful treatment of a variety of clinical (non-)dermatological conditions like alopecies, acne scars, skin burns, skin ulcers, muscle, cartilage, and bone repair, and as an adjuvant in post-surgery wound healing, with obvious benefits in terms of functionality and aesthetic recovery of affected tissues/organs. These indications were well documented, and a large amount of evidence has already been published supporting the efficacy of this method. The primordial principle behind minimally invasive PRP treatments is the usage of the patient's own platelets. The benefits of the autologous transplantation of thrombocytes are significant, representing a fast and economic method that requires only basic equipment and training, and it is biocompatible, thus being a low risk for the patient (infection and immunological reactions can be virtually disregarded). Usually, the structural benefits of applying PRP are attributed to fibroblasts only, as they are considered the most numerous cell population within the interstitium. However, this apparent simplistic explanation is still eluding those different types of interstitial cells (distinct from fibroblasts) that are residing within stromal tissue, e.g., telocytes (TCs). Moreover, dermal TCs have an already documented potential in angiogenesis (extra-cutaneous, but also within skin), and their implication in skin recovery in a few dermatological conditions was attested and described ultrastructurally and immunophenotypically. Interestingly, PRP biochemically consists of a series of growth factors, cytokines, and other molecules, to which TCs have also proven to have a positive expression. Thus, it is attractive to hypothesize and to document any tissular collaboration between cutaneous administered PRP and local dermal TCs in skin recovery/repair/regeneration. Therefore, TCs could be perceived as the missing link necessary to provide a solid explanation of the good results achieved by administering PRP in skin-repairing processes. [ABSTRACT FROM AUTHOR]

Background: Catheter-related bladder discomfort (CRBD) has been found in many patients with urologic surgery. The authors investigated the effect of analgesic-eluting urethral catheters on postoperative CRBD. Methods: 60 subjects scheduled for urologic surgery requiring urethral catheterization were randomized prospectively to one of three groups (control arm, 0.5% ropivacaine 1 mL/h arm [Study 1 arm] and 0.5% ropivacaine 2 mL/h arm [Study 2 arm]; n = 20 each). The incidence and severity of CRBD were evaluated postoperatively at 24 h as primary outcomes. The incidence of adverse events regarding urethral catheter utilization was assessed as a secondary outcome. Results: The CRBD incidence at 24 h postoperatively in the control, study 1 and study 2 arms was 50.0%, 10.0%, and 15.0%, respectively (p = 0.002). The CRBD severity at 24 h postoperatively showed that patients in the study 1 and study 2 arms had significantly less postoperative CRBD than those in the control arm (visual analog score [VAS]; the mean VAS of the control, study 1, and study 2 arms: 2.1 vs. 1.6 vs. 0.9, p = 0.045). Urethral pain regarding catheter was significantly less severe in the study arms than in the control (VAS score: 6.2 vs. 1.5 vs. 1.4, p < 0.001). The severity and incidence of adverse events did not differ significantly among groups (p = 0.287). Peri-catheter leakage was more frequent in the study 2 arm (p = 0.057). Conclusion: The proper usage of a ropivacaine-eluting catheter can not only alleviate CRBD but reduce catheter-related urethral pain in patients with urologic surgery followed by catheterization, without major adverse events. [ABSTRACT FROM AUTHOR]

Stroke remains the second leading cause of death and a major cause of disability worldwide, significantly impacting individuals, families, and healthcare systems. This neurological emergency can be triggered by ischemic events, including small vessel arteriolosclerosis, cardioembolism, and large artery atherothromboembolism, as well as hemorrhagic incidents resulting from macrovascular lesions, venous sinus thrombosis, or vascular malformations, leading to significant neuronal damage. The resultant motor impairment, cognitive dysfunction, and emotional disturbances underscore the urgent need for effective therapeutic interventions. Recent advancements in biomaterials, particularly hydrogels, offer promising new avenues for stroke management. Hydrogels, composed of three-dimensional networks of hydrophilic polymers, are notable for their ability to absorb and retain substantial amounts of water. Commonly used polymers in hydrogel formulations include natural polymers like alginate, chitosan, and collagen, as well as synthetic polymers such as polyethylene glycol (PEG), polyvinyl alcohol (PVA), and polyacrylamide. Their customizable characteristics—such as their porosity, swelling behavior, mechanical strength, and degradation rates—make hydrogels ideal for biomedical applications, including drug delivery, cell delivery, tissue engineering, and the controlled release of therapeutic agents. This review comprehensively explores hydrogel-based approaches to both ischemic and hemorrhagic stroke therapy, elucidating the mechanisms by which hydrogels provide neuroprotection. It covers their application in drug delivery systems, their role in reducing inflammation and secondary injury, and their potential to support neurogenesis and angiogenesis. It also discusses current advancements in hydrogel technology and the significant challenges in translating these innovations from research into clinical practice. Additionally, it emphasizes the limited number of clinical trials utilizing hydrogel therapies for stroke and addresses the associated limitations and constraints, underscoring the need for further research in this field. [ABSTRACT FROM AUTHOR]

The limited reproducibility of the grading of non-muscle invasive papillary urothelial carcinoma (NMIPUC) necessitates the search for more robust image-based predictive factors. In a cohort of 157 NMIPUC patients treated with Bacille Calmette–Guérin (BCG) immunotherapy, we explored the multiple instance learning (MIL)-based classification approach for the prediction of 2-year and 5-year relapse-free survival and the multiple instance survival learning (MISL) framework for survival regression. We used features extracted from image patches sampled from whole slide images of hematoxylin–eosin-stained transurethral resection (TUR) NPMIPUC specimens and tested several patch sampling and feature extraction network variations to optimize the model performance. We selected the model showing the best patient survival stratification for further testing in the context of clinical and pathological variables. MISL with the multiresolution patch sampling technique achieved the best patient risk stratification (concordance index = 0.574, p = 0.010), followed by a 2-year MIL classification. The best-selected model revealed an independent prognostic value in the context of other clinical and pathologic variables (tumor stage, grade, and presence of tumor on the repeated TUR) with statistically significant patient risk stratification. Our findings suggest that MISL-based predictions can improve NMIPUC patient risk stratification, while validation studies are needed to test the generalizability of our models. [ABSTRACT FROM AUTHOR]

Mitochondria are double-membrane organelles that are involved in energy production, apoptosis, and signaling in eukaryotic cells. Several studies conducted over the past decades have correlated mitochondrial dysfunction with various diseases, including cerebral ischemia, myocardial ischemia-reperfusion, and cancer. Mitochondrial transplantation entails importing intact mitochondria from healthy tissues into diseased tissues with damaged mitochondria to rescue the injured cells. In this review, the different mitochondrial transplantation techniques and their clinical applications have been discussed. In addition, the challenges and future directions pertaining to mitochondrial transplantation and its potential in the treatment of diseases with defective mitochondria have been summarized. [ABSTRACT FROM AUTHOR]

We aimed to determine the risk factors for postoperative overactive bladder (OAB) in patients treated with an adjustable trans-obturator male system (ATOMS) for stress incontinence after radical treatment of prostate cancer. A prospective study was performed on 56 patients implanted with an ATOMS for PPI. Clinical and urodynamic information was recorded before and after ATOMS implantation. We built a multivariate model to find out the clinical and urodynamic factors that independently influenced postoperative OAB and the prognostic factors that influenced the efficacy of medical treatment of OAB. We found that the clinical risk factors were the preoperative intensity of urinary incontinence (number of daily pads used and amount of urinary leakage), International Consultation on Incontinence Questionnaire (ICIQ) score, postoperative number of ATOMS adjustments, final cushion volume, and incontinence cure. The urodynamic data associated with OAB were cystometric bladder capacity, voided volume, volume at initial involuntary contraction (IC), maximum flow rate, bladder contractility index (BCI), and urethral resistance (URA). The prognostic factors for the efficacy of oral treatment of OAB were the volume at the first IC (direct relationship) and the maximum abdominal voiding pressure (inverse relationship). The multivariate model showed that the independent clinical risk factors were the daily pad count before the implantation and the ICIQ score at baseline and after treatment. The independent urodynamic data were the volume at the first IC (inverse relationship) and the URA value (direct relationship). Both predictive factors of treatment efficacy were found to be independent. Detrusor overactivity plays an important role in postoperative OAB, although other urodynamic and clinical factors such as the degree of urethral resistance and abdominal strength may influence this condition. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article on cell therapy for anal sphincter incontinence. The authors have made corrections to the citations and reference numbers, as well as updated the references in Table 1. Table 3 provides information on the characteristics of primary cells proposed for cell therapy of anal sphincter incontinence. The document also discusses the use of cell therapy for anal sphincter injury, including various studies and clinical trials. It highlights the practical considerations and challenges associated with cell therapy, as well as the need for further research in this area. Additionally, the document is part of a collection of articles exploring regenerative therapies for anal sphincter injury and fecal incontinence, providing valuable insights for researchers and healthcare professionals. [Extracted from the article]

Prostate cancer (PCa) is a low tumor mutational burden (TMB) cancer with a poor response to immunotherapy. Nonetheless, immunotherapy can be useful, especially in metastatic castration-resistant PCa (mCRPC). Increased cytotoxic T lymphocytes (CTLs) density is correlated with a shorter overall survival (OS), an early biochemical relapse, and a generally poor PCa prognosis. An increased number of CCR4+ regulatory T cells (CCR4 + Tregs) relates to a higher Gleason score or earlier progression. The same therapeutic options are available for renal transplant recipients (RTRs) as for the population, with a comparable functional and oncological outcome. Radical retropubic prostatectomy (RRP) is the most common method of radical treatment in RTRs. Brachytherapy and robot-assisted radical prostatectomy (RARP) seem to be promising therapies. Further studies are needed to assess the need for prostatectomy in low-risk patients before transplantation. The rate of adverse pathological features in RTRs does not seem to differ from those observed in the non-transplant population and the achieved cancer control seems comparable. The association between PCa and transplantation is not entirely clear. Some researchers indicate a possible association between a more frequent occurrence of PCa and a worse prognosis in advanced or metastatic PCa. However, others claim that the risk and survival prognosis is comparable to the non-transplant population. [ABSTRACT FROM AUTHOR]

Today, the various abilities that nurses require to meet patients' healthcare needs adequately are all affected by AI-enabled systems. This research used an experimental study design in which 60 subjects were randomly assigned to either an experimental (AI image e-book guidance) group or a control (text paper guidance) group after meeting the admission conditions and agreeing to participate in the study. It was proven that providing AI image e-book guidance before surgery significantly changed the behavior of patients and promoted relief of urinary catheter discomfort through self-efficacy to reduce urinary catheter pain after surgery (p < 0.001). It was found that providing AI image e-book guidance can shorten the time for health education and provide patients with repeated medical education and familiarity with health guidance, which can help to address the important clinical service demand issue and the shortage of nursing staff. [ABSTRACT FROM AUTHOR]

This study aims to activate the external urethral sphincter (EUS), which plays a critical role in micturition control, through optogenetics and to determine its potential contribution to the stabilization of sensitized micturition activity. The viral vector (AAV2/8-CMV-hChR2(H134R)-EGFP) is utilized to introduce light-gated ion channels (hChR2/H134R) into the EUS of wild-type C57BL/6 mice. Following the induction of sensitized micturition activity using weak acetic acid (0.1%) in anesthetized mice, optical stimulation of the EUS muscle tissue expressing channel rhodopsin is performed using a 473 nm laser light delivered through optical fibers, and the resulting changes in muscle activation and micturition activity are examined. Through EMG (electromyography) measurements, it is confirmed that optical stimulation electrically activates the EUS muscle in mice. Analysis of micturition activity using cystometry reveals a 70.58% decrease in the micturition period and a 70.27% decrease in the voiding volume due to sensitized voiding. However, with optical stimulation, the micturition period recovers to 101.49%, and the voiding volume recovered to 100.22%. Stimulation of the EUS using optogenetics can alleviate sensitized micturition activity and holds potential for application in conjunction with other micturition control methods. [ABSTRACT FROM AUTHOR]

Simple Summary: Stress urinary incontinence is a common sequela in men after radical prostatectomy for the treatment of prostate cancer. Varying degrees of post-prostatectomy incontinence will present after surgery and surgical treatment may be recommended after one year. The severity of incontinence can range from less than 1 urinary pads per day (PPD) to more than 5 PPD. Treatments for mild incontinence include the male sling while more severe incontinence often requires an artificial urinary sphincter (AUS). Currently, patients with moderate incontinence are treated with either a sling or AUS with variable results. In this paper, we reviewed recent research to demonstrate that AUS should be considered first-line for moderate incontinence. While patients and physicians may be hesitant to proceed with an implantable device, patients achieved better continence rates and overall quality of life when they underwent AUS placement for moderate post-prostatectomy incontinence. Male urinary incontinence is a common complication after radical prostatectomy. The severity of incontinence can be assessed in various ways and helps determine the best surgical intervention to restore continence. While most patients with mild incontinence receive a sling and those with severe incontinence receive an artificial urinary sphincter (AUS), there are no clear guidelines on how to manage patients with moderate post-prostatectomy incontinence (PPI). Our discussion will focus on the current literature, which demonstrates that an AUS should be considered first-line in men with moderate PPI despite perceived concerns over complications and reintervention rates. [ABSTRACT FROM AUTHOR]

Wound healing is a complex and meticulously orchestrated process involving multiple phases and cellular interactions. This narrative review explores the intricate mechanisms behind wound healing, emphasizing the significance of cellular processes and molecular factors. The phases of wound healing are discussed, focusing on the roles of immune cells, growth factors, and extracellular matrix components. Cellular shape alterations driven by cytoskeletal modulation and the influence of the 'Formin' protein family are highlighted for their impact on wound healing processes. This review delves into the use of absorbable meshes in wound repair, discussing their categories and applications in different surgical scenarios. Interleukins (IL-2 and IL-6), CD31, CD34, platelet rich plasma (PRP), and adipose tissue-derived mesenchymal stem cells (ADSCs) are discussed in their respective roles in wound healing. The interactions between these factors and their potential synergies with absorbable meshes are explored, shedding light on how these combinations might enhance the healing process. Recent advances and challenges in the field are also presented, including insights into mesh integration, biocompatibility, infection prevention, and postoperative complications. This review underscores the importance of patient-specific factors and surgical techniques in optimizing mesh placement and healing outcomes. As wound healing remains a dynamic field, this narrative review provides a comprehensive overview of the current understanding and potential avenues for future research and clinical applications. [ABSTRACT FROM AUTHOR]

Stress urinary incontinence is still a frequent problem for women and men, which leads to pronounced impairment of the quality of life and withdrawal from the social environment. Modern diagnostics and therapy improved the situation for individuals affected. But there are still limits, including the correct diagnosis of incontinence and its pathophysiology, as well as the therapeutic algorithms. In most cases, patients are treated with a first-line regimen of drugs, possibly in combination with specific exercises and electrophysiological stimulation. When conservative options are exhausted, minimally invasive surgical therapies are indicated. However, standard surgeries, especially the application of implants, do not pursue any causal therapy. Non-absorbable meshes and ligaments have fallen into disrepute due to complications. In numerous countries, classic techniques such as colposuspension have been revived to avoid implants. Except for tapes in the treatment of stress urinary incontinence in women, the literature on randomized controlled studies is insufficient. This review provides an update on pharmacological and surgical treatment options for stress urinary incontinence; it highlights limitations and formulates wishes for the future from a clinical perspective. [ABSTRACT FROM AUTHOR]

Mitochondria are essential organelles for maintaining intracellular homeostasis. Their dysfunction can directly or indirectly affect cell functioning and is linked to multiple diseases. Donation of exogenous mitochondria is potentially a viable therapeutic strategy. For this, selecting appropriate donors of exogenous mitochondria is critical. We previously demonstrated that ultra-purified bone marrow-derived mesenchymal stem cells (RECs) have better stem cell properties and homogeneity than conventionally cultured bone marrow-derived mesenchymal stem cells. Here, we explored the effect of contact and noncontact systems on three possible mitochondrial transfer mechanisms involving tunneling nanotubes, connexin 43 (Cx43)-mediated gap junction channels (GJCs), and extracellular vesicles (Evs). We show that Evs and Cx43-GJCs provide the main mechanism for mitochondrial transfer from RECs. Through these two critical mitochondrial transfer pathways, RECs could transfer a greater number of mitochondria into mitochondria-deficient (ρ0) cells and could significantly restore mitochondrial functional parameters. Furthermore, we analyzed the effect of exosomes (EXO) on the rate of mitochondrial transfer from RECs and recovery of mitochondrial function. REC-derived EXO appeared to promote mitochondrial transfer and slightly improve the recovery of mtDNA content and oxidative phosphorylation in ρ0 cells. Thus, ultrapure, homogenous, and safe stem cell RECs could provide a potential therapeutic tool for diseases associated with mitochondrial dysfunction. [ABSTRACT FROM AUTHOR]

Radiation therapy (RT) in the management of pelvic cancers remains a clinical challenge to urologists given the sequelae of urethral stricture disease secondary to fibrosis and vascular insults. The objective of this review is to understand the physiology of radiation-induced stricture disease and to educate urologists in clinical practice regarding future prospective options clinicians have to deal with this condition. The management of post-radiation urethral stricture consists of conservative, endoscopic, and primary reconstructive options. Endoscopic approaches remain an option, but with limited long-term success. Despite concerns with graft take, reconstructive options such as urethroplasties in this population with buccal grafts have shown long-term success rates ranging from 70 to 100%. Robotic reconstruction is augmenting previous options with faster recovery times. Radiation-induced stricture disease is challenging with multiple interventions available, but with successful outcomes demonstrated in various cohorts including urethroplasties with buccal grafts and robotic reconstruction. [ABSTRACT FROM AUTHOR]

Simple Summary: Conventional natural killer (NK)-based anticancer immunotherapy has a limitation: a culture period of approximately 2 weeks is required to increase the number and activity of NK cells. By transferring functional allogeneic mitochondria into NK cells, we demonstrated that the activity of NK cells and their cytotoxicity were significantly enhanced. This approach could potentially offer a timely therapeutic strategy for cancer treatment without the need for in vitro culture, which can be time-consuming and costly. An in vitro culture period of at least 2 weeks is required to produce sufficient natural killer (NK) cells for immunotherapy, which are the key effectors in hematological malignancy treatment. Mitochondrial damage and fragmentation reduce the NK cell immune surveillance capacity. Thus, we hypothesized that the transfer of healthy mitochondria to NK cells could enhance their anticancer effects. Allogeneic healthy mitochondria isolated from WRL-68 cells were transferred to NK cells. We evaluated NK cells' proliferative capacity, cell cycle, and cytotoxic capacity against various cancer cell types by analyzing specific lysis and the cytotoxic granules released. The relationship between the transferred allogenic mitochondrial residues and NK cell function was determined. After mitochondrial transfer, the NK cell proliferation rate was 1.2-fold higher than that of control cells. The mitochondria-treated NK cells secreted a 2.7-, 4.1-, and 5-fold higher amount of granzyme B, perforin, and IFN-γ, respectively, when co-cultured with K562 cells. The specific lysis of various solid cancer cells increased 1.3–1.6-fold. However, once allogeneic mitochondria were eliminated, the NK cell activity returned to the pre-mitochondrial transfer level. Mitochondria-enriched NK cells have the potential to be used as a novel solid cancer treatment agent, without the need for in vitro cytokine-induced culture. [ABSTRACT FROM AUTHOR]

Erectile dysfunction (ED) is a common and feared complication of radical prostatectomy (RP) for prostate cancer. Recently, tissue engineering for post-prostatectomy ED has been attempted in which controlled interactions between cells, growth factors, and the extracellular matrix (ECM) are important for the structural integrity if nerve regeneration. In this study, we evaluated the effects of a biomechanical ECM patch on the morphology and behavior of human bone marrow-derived mesenchymal stem cells (hBMSCs) in a bilateral cavernous nerve injury (BCNI) rat model. The ECM patch, made of decellularized human fibroblast-derived ECM (hFDM) and a biocompatible polyvinyl alcohol (PVA) hydrogel, was tested with human bone marrow-derived mesenchymal stem cells (hBMSCs) on a bilateral cavernous nerve injury (BCNI) rat model. In vitro analysis showed that the hFDM/PVA + hBMSCs patches significantly increased neural development markers. In vivo experiments demonstrated that the rats treated with the hFDM/PVA patch had higher ICP/MAP ratios, higher ratios of smooth muscle to collagen, increased nNOS content, higher levels of eNOS protein expression, and higher cGMP levels compared to the BCNI group. These results indicate that the hFDM/PVA patch is effective in promoting angiogenesis, smooth muscle regeneration, and nitrergic nerve regeneration, which could contribute to improved erectile function in post-prostatectomy ED. [ABSTRACT FROM AUTHOR]

Erectile dysfunction (ED) is the inability to get and maintain an adequate penile erection for satisfactory sexual intercourse. Due to its negative impacts on men's life quality and increase during aging (40% of men between 40 and 70 years), ED has always attracted researchers of different disciplines, from urology, andrology and neuropharmacology to regenerative medicine, and vascular and prosthesis implant surgery. Locally and/or centrally acting drugs are used to treat ED, e.g., phosphodiesterase 5 inhibitors (first in the list) given orally, and phentolamine, prostaglandin E1 and papaverine injected intracavernously. Preclinical data also show that dopamine D4 receptor agonists, oxytocin and α-MSH analogues may have a role in ED treatment. However, since pro-erectile drugs are given on demand and are not always efficacious, new strategies are being tested for long lasting cures of ED. These include regenerative therapies, e.g., stem cells, plasma-enriched platelets and extracorporeal shock wave treatments to cure damaged erectile tissues. Although fascinating, these therapies are laborious, expensive and not easily reproducible. This leaves old vacuum erection devices and penile prostheses as the only way to get an artificial erection and sexual intercourse with intractable ED, with penile prosthesis used only by accurately selected patients. [ABSTRACT FROM AUTHOR]

The mitochondria play a crucial role in cellular metabolism, reactive oxygen species (ROS) production, and apoptosis. Aberrant mitochondria can cause severe damage to the cells, which have established a tight quality control for the mitochondria. This process avoids the accumulation of damaged mitochondria and can lead to the release of mitochondrial constituents to the extracellular milieu through mitochondrial extracellular vesicles (MitoEVs). These MitoEVs carry mtDNA, rRNA, tRNA, and protein complexes of the respiratory chain, and the largest MitoEVs can even transport whole mitochondria. Macrophages ultimately engulf these MitoEVs to undergo outsourced mitophagy. Recently, it has been reported that MitoEVs can also contain healthy mitochondria, whose function seems to be the rescue of stressed cells by restoring the loss of mitochondrial function. This mitochondrial transfer has opened the field of their use as potential disease biomarkers and therapeutic tools. This review describes this new EVs-mediated transfer of the mitochondria and the current application of MitoEVs in the clinical environment. [ABSTRACT FROM AUTHOR]

Background: The anatomy curriculum has undergone considerable reductions in class time, resulting in decreased student anatomical knowledge retention and confidence during their surgical rotations. To counter this deficit in anatomy knowledge, a clinical anatomy mentorship program (CAMP) was developed by fourth-year medical student leaders and staff mentors in a near-peer teaching fashion prior to the surgical clerkship. This study analyzed the impact this program had on third-year medical students (MS3s) self-assessed anatomical knowledge and confidence in the operating room on the Breast Surgical Oncology rotation after this near-peer program. Methods: A single-center prospective survey study was performed at an academic medical center. Pre- and post-program surveys were administered to all students who participated in the CAMP and rotated on the breast surgical oncology (BSO) service during the surgery clerkship rotation. A control group of individuals who did not rotate on the CAMP was established, and this group was administered a retrospective survey. A 5-point Likert scale was used to assess surgical anatomy knowledge, confidence in the operating room, and comfort in assisting in the operating room. Control group versus post-CAMP intervention group and pre- versus post-CAMP intervention groups survey results were compared using the Student's t-test with a p-value of <0.05 statistically significant. Results: All CAMP students rated their surgical anatomy knowledge (p < 0.01), confidence in the operating room (p < 0.01), and comfort in assisting in the operating room (p < 0.01) as greater than those who did not participate in the program. Additionally, the program improved the ability of third-year medical students to prepare for operating room cases going into their third-year breast surgical oncology clerkship (p < 0.03). Conclusions: This near-peer surgical education model appears to be an effective way to prepare third-year medical students for the breast surgical oncology rotation during the surgery clerkship by improving anatomic knowledge and student confidence. The program can serve as a template for medical students, surgical clerkship directors, and other faculty interested in efficiently expanding surgical anatomy at their institution. [ABSTRACT FROM AUTHOR]

The management of sexual complications after treatment of localized prostate cancer, such as erectile dysfunction, changes in the length of the penis, pain during sexual intercourse, and lack of orgasm, is still an unsolved problem with an important impact on patients' quality of life. In this review, we summarize the current scientific literature about the rehabilitation of erectile dysfunction after prostate cancer treatment. The therapy for penile rehabilitation includes different types of treatments: the combination of phosphodiesterase type 5 inhibitors (PDE5-I) and the vacuum erectile device (VED) are considered first-line treatment options. When therapy begins, the duration of treatment, the dosage and the drug used all play very important roles in the treatment outcome. Intracavernous injection (ICI) therapy represents the second-line option for patients ineligible for PDE5-I therapy. Technological development has led to the emergence of devices for the stimulation of the penis without the use of drugs, such as penile vibratory stimulation (PVS) for stimulation of ejaculation in spinal cord injury and low-intensity extracorporeal shockwave therapy (LIESWT). The rapid diffusion of the latter, thanks to its easy use, attains good results without side effects. The panorama of penile rehabilitation after PC treatments is vast and many studies are needed, especially on new technologies, to find the best therapeutic regimen possible, personalized to the patient's characteristics and the type of treatment for PC. [ABSTRACT FROM AUTHOR]

A radical prostatectomy is frequently used as the first-line treatment for men with prostate cancer. Persistent urinary incontinence after surgery is one of the most severe adverse events. We report the results of a comprehensive literature search focused on post-prostatectomy urinary incontinence (PPI), performed by a panel of experts on non-neurogenic lower urinary tract symptoms. The data on the prevalence and timing of PPI are very heterogeneous. The etiology of PPI can be multifactorial and mainly dependent on patient characteristics, lower urinary tract function or surgical issues. The medical history with a physical examination, the use of validated questionnaires with a voiding diary and pad tests are determinants in identifying the contributing factors and choosing the right treatment. Lifestyle intervention and urinary containment are the most frequently used strategies for the conservative management of PPI, while antimuscarinics, beta-3 agonists and duloxetine (off-label) are drugs indicated to manage PPI with a concomitant overactive bladder. Surgical therapies for the management of post-prostatectomy SUI include non-adjustable trans-obturator slings in men with mild-to-moderate incontinence and an artificial urinary sphincter in men with moderate-to-severe incontinence. [ABSTRACT FROM AUTHOR]

Background: The improvement of absent or partial response in the medical treatment of erectile dysfunction (ED) has led to the development of minimally invasive new treatment modalities in the field of regenerative medicine. Methods: A literature review on stem cell therapy for the treatment of ED was performed. We searched for the terms "erectile dysfunction" and "stem cell therapy" in PubMed and Clinicaltrials.gov. Literature searching was conducted in English and included articles from 2010 to 2022. Results: New treatment modalities for ED involving stem cell therapy are not only conceived with a curative intent but also aim to avoid unnecessary adverse effects. Several sources of stem cells have been described, each with unique characteristics and potential applications, and different delivery methods have been explored. A limited number of interventional studies over the past recent years have provided evidence of a safety profile in their use and promising results for the treatment of ED, although there are not enough studies to generate an appropriate protocol, dose or cell lineage, or to determine a mechanism of action. Conclusions: Stem cell therapy is a novel treatment for ED with potential future applications. However, most urological societies agree that further research is required to conclusively prove its potential benefit. [ABSTRACT FROM AUTHOR]

Stress urinary incontinence is a common disease in middle-aged and elderly women, which seriously affects the physical and mental health of the patients. For this reason, researchers have carried out a large number of studies on stress urinary incontinence. At present, it is believed that the pathogenesis of the disease is mainly due to changes related to age, childbirth, obesity, constipation and other risk factors that induce changes in the urinary control anatomy, including the anatomical factors of the urethra itself, the anatomical factors around the urethra and the anatomical factors of the pelvic nerve. The combined actions of a variety of factors lead to the occurrence of stress urinary incontinence. This review aims to summarize the anatomical pathogenesis of stress urinary incontinence from the above three perspectives. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the outcomes of re-adjustable male slings in pa-tients with postoperative stress urinary incontinence (SUI) following radical prostatectomy (RP). We retrospectively analyzed 18 patients with SUI following RP for prostate cancer, who were treated with re-adjustable male slings from January 2016 to December 2021. The clinical outcomes were evaluated based on daily pad usage and urodynamic studies, both preoperatively and post-operatively. The degree of SUI was categorized as either mild, moderate, or severe. Success was defined as no more pad use or significantly decreased pad use. Complications were classified ac-cording to the Clavien–Dindo system. The mean age of patients was 70.4 ± 5.9 years, and 61.1% of cases were diagnosed as locally advanced prostate cancer. Mild, moderate, and severe SUI were reported as 33.3%, 50.0%, and 16.7%, respectively. The average daily pad use after RP was 3.3 pads and there was a significant reduction in the number of daily pads used after the re-adjustable male sling procedure (3.3 vs. 1.3; p = 0.002). Overall, the operation was considered successful in 11 pa-tients (61.1%), 1 case showed improvement (5.6%), and it was considered unsuccessful in 6 patients (33.3%). Impressively, in the severe incontinence subgroup (three patients), one (33.3%) had im-provement and one (33.3%) had success. Transient perineal discomfort after the operation was the most common complaint. However, two patients had severe complications with bowel injury during sling implantation (Clavien–Dindo grade III). The re-adjustable male sling system was an efficient surgical treatment option for post-RP SUI, even in a locally advanced disease dominant population. One should pay attention to the complication of bowel perforation during surgery. [ABSTRACT FROM AUTHOR]

Background and Objectives: This study aims to elucidate the positive rate and the clinicopathological significance of surgical margin after radical prostatectomy (RP) through a meta-analysis. Materials and Methods: This meta-analysis finally used 59 studies, including the information about the positive surgical margin (PSM) and those clinicopathological significances after RP. The subgroup analysis for the estimated rates of PSM was evaluated based on types of surgery, grade groups, and pathological tumor (pT) stages. We compared the clinicopathological correlations between positive and negative surgical margins (NSM). Results: The estimated PSM rate was 25.3% after RP (95% confidence interval [CI] 21.9–29.0%). The PSM rates were 26.0% (95% CI 21.5–31.1%) 28.0% (95% CI 20.2–37.5%) in robot-assisted RP and nerve-sparing RP, respectively. The PSM rate was significantly higher in high-grade groups than in low-grade groups. In addition, the higher pT stage subgroup had a high PSM rate compared to the lower pT stage subgroups. Patients with PSM showed significantly high PSA levels, frequent lymphovascular invasion, lymph node metastasis, and extraprostatic extension. Biochemical recurrences (BCRs) were 28.5% (95% CI 21.4–36.9%) and 11.8% (95% CI 8.1–16.9%) in PSM and NSM subgroups, respectively. Patients with PSM showed worse BCR-free survival than those with NSM (hazard ratio 2.368, 95% CI 2.043–2.744%). Conclusions: Our results showed that PSM was significantly correlated with worse clinicopathological characteristics and biochemical recurrence-free survival. Among the results in preoperative evaluations, grade group and tumor stage are useful for the prediction of PSM. [ABSTRACT FROM AUTHOR]

About 35% of patients affected by erectile dysfunction (ED) do not respond to oral phosphodiesterase-5 inhibitors (PDE5i) and more severe vasculogenic refractory ED affects diabetic patients. Innovative approaches, such as regenerative therapies, including stem cell therapy (SCT) and platelet-rich plasma (PRP), are currently under investigation. Recent data point out that the regenerative capacity of stem cells is strongly influenced by local immune responses, with macrophages playing a pivotal role in the injury response and as a coordinator of tissue regeneration, suggesting that control of the immune response could be an appealing approach in regenerative medicine. A new generation of autologous cell therapy based on immune cells instead of stem cells, which could change regenerative medicine for good, is discussed. Increasing safety and efficacy data are coming from clinical trials using peripheral blood mononuclear cells to treat no-option critical limb ischemia and diabetic foot. In this review, ongoing phase 1/phase 2 stem cell clinical trials are discussed. In addition, we examine the mechanism of action and rationale, as well as propose a new generation of regenerative therapies, evolving from typical stem cell or growth factor to immune cell-based medicine, based on autologous peripheral blood mononuclear cells (PBMNC) concentrates for the treatment of ED. [ABSTRACT FROM AUTHOR]

Background and Objectives: As the use of sugammadex for reversing neuromuscular blockade during general anesthesia increases, additional effects of sugammadex have been reported compared to cholinesterase inhibitors. Here, we compare the incidence of postoperative catheter-related bladder discomfort (CRBD) between sugammadex and pyridostigmine/glycopyrrolate treatments for reversing neuromuscular blockade. Materials and Methods: We retrospectively analyzed patients aged ≥ 18 years who underwent surgery under general anesthesia, received sugammadex or pyridostigmine with glycopyrrolate to reverse neuromuscular blockade, and had a urinary catheter in the post-anesthesia care unit between March 2019 and February 2021. After applying the exclusion criteria, 1179 patients were included in the final analysis. The incidence and severity of CRBD were collected from post-anesthesia recovery records. Results: The incidence was 13.7% in the sugammadex group (n = 211) and 24.7% in the pyridostigmine group (n = 968). Following propensity score matching, 211 patients each were included in the pyridostigmine and sugammadex matched group (absolute standardized difference (ASD), 0.01–0.05). Compared to the pyridostigmine group, the odds ratio for CRBD occurring in the sugammadex group was 0.568 (95% confidential interval, 0.316–1.021, p = 0.059). Conclusions: Sugammadex has a similar effect on the occurrence of postoperative CRBD compared with pyridostigmine. [ABSTRACT FROM AUTHOR]

Erectile dysfunction (ED) is a significant cause of reduced quality of life in men and their partners. Cavernous nerve injury (CNI) during pelvic surgery results in ED in greater than 50% of patients, regardless of additional patient factors. ED related to CNI is difficult to treat and typically poorly responsive to first- and second-line therapeutic options. Recently, a significant amount of research has been devoted to exploring neuroprotective and neuroregenerative approaches to salvage erectile function in patients with CNI. In addition, therapeutic options such as neuregulins, immunophilin ligands, gene therapy, stem cell therapy and novel surgical strategies, have shown benefit in pre-clinical, and limited clinical studies. In the era of personalized medicine, these new therapeutic technologies will be the future of ED treatment and are described in this review. [ABSTRACT FROM AUTHOR]

The major challenge for stem cell translation regenerative medicine is the regeneration of damaged tissues by creating biological substitutes capable of recapitulating the missing function in the recipient host. Therefore, the current paradigm of tissue engineering strategies is the combination of a selected stem cell type, based on their capability to differentiate toward committed cell lineages, and a biomaterial, that, due to own characteristics (e.g., chemical, electric, mechanical property, nano-topography, and nanostructured molecular components), could serve as active scaffold to generate a bio-hybrid tissue/organ. Thus, effort has been made on the generation of in vitro tissue engineering modeling. Here, we present an in vitro model where human adipose stem cells isolated from lipoaspirate adipose tissue and breast adipose tissue, cultured on polymeric INTEGRA® Meshed BilayerWound Matrix (selected based on conventional clinical applications) are evaluated for their potential application for reconstructive surgery toward bone and adipose tissue. We demonstrated that human adipose stem cells isolated from lipoaspirate and breast tissue have similar stemness properties and are suitable for tissue engineering applications. Finally, the overall results highlighted lipoaspirate adipose tissue as a good source for the generation of adult adipose stem cells. [ABSTRACT FROM AUTHOR]

In eukaryotic cells, mitochondria are self-reproducing organelles with their own DNA and they play a central role in adenosine triphosphate (ATP) synthesis by respiration. Increasing evidence indicates that mitochondria also have critical and multiple functions in the initiation of cell differentiation, cell-type determination, cell movement, and pattern formation. This has been most strikingly realized in development of the cellular slime mold Dictyostelium. For example, the expression of the mitochondrial ribosomal protein S4 (mt-rps4) gene is required for the initial differentiation. The Dictyostelium homologue (Dd-TRAP1) of TRAP-1 (tumor necrosis receptor-associated protein 1), a mitochondrial molecular chaperone belonging to the Hsp90 family, allows the prompt transition of cells from growth to differentiation through a novel prestarvation factor (PSF-3) in growth medium. Moreover, a cell-type-specific organelle named a prespore-specific vacuole (PSV) is constructed by mitochondrial transformation with the help of the Golgi complex. Mitochondria are also closely involved in a variety of cellular activities including CN-resistant respiration and apoptosis. These mitochondrial functions are reviewed in this article, with special emphasis on the regulation of Dictyostelium development. [ABSTRACT FROM AUTHOR]

The blood–brain barrier (BBB) is fundamental in maintaining central nervous system (CNS) homeostasis by regulating the chemical environment of the underlying brain parenchyma. Brain endothelial cells (BECs) constitute the anatomical and functional basis of the BBB. Communication between adjacent BECs is critical for establishing BBB integrity, and knowledge of its nanoscopic landscape will contribute to our understanding of how juxtaposed zones of tight-junction protein interactions between BECs are aligned. The review discusses and critiques types of nanostructures contributing to the process of BBB genesis. We further critically evaluate earlier findings in light of novel high-resolution electron microscopy descriptions of nanoscopic tubules. One such phenotypic structure is BEC cytoplasmic projections, which, early in the literature, is postulated as brain capillary endothelial cilia, and is evaluated and compared to the recently discovered nanotubules (NTs) formed in the paracellular spaces between BECs during barrier-genesis. The review attempts to elucidate a myriad of unique topographical ultrastructures that have been reported to be associated with the development of the BBB, viz., structures ranging from cilia to BEC tunneling nanotubules (TUNTs) and BEC tethering nanotubules (TENTs). [ABSTRACT FROM AUTHOR]

Stem cells (SC) are largely known for their potential to restore damaged tissue through various known mechanisms. Among these mechanisms is their ability to transfer healthy mitochondria to injured cells to rescue them. This mitochondrial transfer plays a critical role in the healing process. To determine the optimal parameters for inducing mitochondrial transfer between cells, we assessed mitochondrial transfer as a function of seeding density and in two-dimensional (2D) and semi three-dimensional (2.5D) culture models. Since mitochondrial transfer can occur through direct contact or secretion, the 2.5D culture model utilizes collagen to provide cells with a more physiologically relevant extracellular matrix and offers a more realistic representation of cell attachment and movement. Results demonstrate the dependence of mitochondrial transfer on cell density and the distance between donor and recipient cell. Furthermore, the differences found between the transfer of mitochondria in 2D and 2.5D microenvironments suggest an optimal mode of mitochondria transport. Using these parameters, we explored the effects on mitochondrial transfer between SCs and tumorigenic cells. HEK293 (HEK) is an immortalized cell line derived from human embryonic kidney cells which grow rapidly and form tumors in culture. Consequently, HEKs have been deemed tumorigenic and are widely used in cancer research. We observed mitochondrial transfer from SCs to HEK cells at significantly higher transfer rates when compared to a SC–SC co-culture system. Interestingly, our results also revealed an increase in the migratory ability of HEK cells when cultured with SCs. As more researchers find co-localization of stem cells and tumors in the human body, these results could be used to better understand their biological relationship and lead to enhanced therapeutic applications. [ABSTRACT FROM AUTHOR]

Jatropha macrantha Müll Arg. L is also known as "huanarpo macho" and used in the Peruvian traditional medicine as an aphrodisiac and erectile dysfunction (ED). The aim of this study was to determine the phytochemical constituents in leaves and stems ethyl acetate fraction (LEAF and SEAF) of J. macrantha and to compare the antioxidant activity and the ameliorative effect on ketamine-induced erectile dysfunction in rats. The phytochemical constituents were determined by LC-ESI-MS/MS, the total phenolic compounds and total flavonoids (TPC and TF) by Folin-Ciocalteu and aluminum chloride, respectively. The antioxidant activity was determined by DPPH, ABTS, and FRAP assays. Experimental groups were divided as follows: I: negative control; II: positive control (ketamine at 50 mg/ kg/d); III: sildenafil 5 mg/kg; IV, V, VI: LEAF at 25, 50 and 100 mg/kg, respectively, and VII, VIII, IX: SEAF at 25, 50, and 100 mg/kg, respectively. The phytochemical analysis revealed the presence mainly of coumarins, flavonoids, phenolic acids, and terpenes. TPC of LEAF and SEAF were 359 ± 5.21 mg GAE/g and 306 ± 1.93 mg GAE/g, respectively; TF in LEAF and SEAF were 23.7 ± 0.80 mg EQ/g, and 101 ± 1.42 mg EQ/g, respectively. The DPPH, ABTS, FRAP in SEAF were 647 ± 3.27; 668 ± 2.30; and 575 ± 2.86 μmol TE/g, respectively, whilst LEAF showed 796 ± 3.15; 679 ± 0.85; and 806 ± 3.42 μmol TE/g, respectively. Regarding sexual behavior, LEAF showed a better effect in mount frequency, intromission frequency, ejaculation frequency, mount latency, intromission latency, ejaculatory latency, and post ejaculatory latency than SEAF. As conclusion, LEAF of J. macrantha at 50 mg/kg showed a better effect on sexual behavior in male rats with erectile dysfunction than SEAF but not higher than sildenafil. [ABSTRACT FROM AUTHOR]

Background: Erectile dysfunction (ED) remains an emotional wrench to patients and a therapeutic challenge to urologists in andrology clinics worldwide. This is, in part, related to refraction to, or transient effect of phosphodiesterase 5 inhibitors (PDE5i), coupled with patients' dissatisfaction with this treatment modality. Low-intensity extracorporeal shockwave therapy (Li-ESWT) is an evolving treatment option, with promising curative potential. Current international guidelines are inconclusive, bear weak recommendation strength, and lack ethnogeographic consensus. Objectives: This study evaluated the safety, efficacy, and effect duration of Li-ESWT, as well as exploring disease-associated determinants of treatment success in Taiwanese males with ED. Methods: A cohort of 69 eligible cases treated with 12 sessions of Li-ESWT and followed up for at least 12 months after treatment, between January 2018 and December 2019 at our medical facility, was used. The present single-center, retrospective, non-randomized, single-arm study employed standardized erectile function evaluation indices, namely, the five-item International Index of Erectile Function (IIEF-5) and Erection Hardness Score (EHS). Clinicopathological analyses of selected variables and comparative analyses of time-phased changes in the EF indices relative to baseline values were performed. Evaluation of treatment success was based on minimal clinically important difference (MCID), using a binomial logistic regression model. Results: The median age and duration of ED for our Taiwanese cohort were 55 years and 12 months, respectively, and an average of 31.3% presented with co-morbidities. The mean improvement in IIEF-5, EHS, and quality of life (QoL) domain scores relative to the baseline values was statistically very significant (p < 0.001) at all indicated follow-up time-points. When stratified, Taiwanese patients with severe and moderate ED benefited more from Li-ESWT, compared with those in the mild or mild-to-moderate group. Patients' pre-Li-ESWT PDE5i response status was not found to significantly influence Li-ESWT response. Univariate analysis showed that age > 45 years (p = 0.04), uncontrolled diabetes mellitus (p = 0.04), and uncontrolled hyperlipidemia (p = 0.01) were strongly associated with Li-ESWT efficacy; however, only age > 45 years (p = 0.04) and uncontrolled hyperlipidemia (p = 0.03) were found to be independent negative predictors of Li-ESWT success by the multivariate logistic model. Follow-up was uneventful, with no treatment-related adverse events or side effects reported. Of the treated patients, 86.1% indicated satisfaction with the treatment regimen, and over 90% indicated they would recommend the same therapy to others. Conclusions: Li-ESWT is a safe and efficacious therapeutic modality for Taiwanese patients with ED. Uncontrolled hyperlipidemia and age > 45 years are independent negative predictors of treatment success for this cohort. [ABSTRACT FROM AUTHOR]

In recent years, many promising nanotechnological approaches to biomedical research have been developed in order to increase implementation of regenerative medicine and tissue engineering in clinical practice. In the meantime, the use of nanomaterials for the regeneration of diseased or injured tissues is considered advantageous in most areas of medicine. In particular, for the treatment of cardiovascular, osteochondral and neurological defects, but also for the recovery of functions of other organs such as kidney, liver, pancreas, bladder, urethra and for wound healing, nanomaterials are increasingly being developed that serve as scaffolds, mimic the extracellular matrix and promote adhesion or differentiation of cells. This review focuses on the latest developments in regenerative medicine, in which iron oxide nanoparticles (IONPs) play a crucial role for tissue engineering and cell therapy. IONPs are not only enabling the use of non-invasive observation methods to monitor the therapy, but can also accelerate and enhance regeneration, either thanks to their inherent magnetic properties or by functionalization with bioactive or therapeutic compounds, such as drugs, enzymes and growth factors. In addition, the presence of magnetic fields can direct IONP-labeled cells specifically to the site of action or induce cell differentiation into a specific cell type through mechanotransduction. [ABSTRACT FROM AUTHOR]

Anal sphincter incontinence is a chronic disease, which dramatically impairs quality of life and induces high costs for the society. Surgery, considered as the best curative option, shows a disappointing success rate. Stem/progenitor cell therapy is pledging, for anal sphincter incontinence, a substitute to surgery with higher efficacy. However, the published literature is disparate. Our aim was to perform a review on the development of cell therapy for anal sphincter incontinence with critical analyses of its pitfalls. Animal models for anal sphincter incontinence were varied and tried to reproduce distinct clinical situations (acute injury or healed injury with or without surgical reconstruction) but were limited by anatomical considerations. Cell preparations used for treatment, originated, in order of frequency, from skeletal muscle, bone marrow or fat tissue. The characterization of these preparations was often incomplete and stemness not always addressed. Despite a lack of understanding of sphincter healing processes and the exact mechanism of action of cell preparations, this treatment was evaluated in 83 incontinent patients, reporting encouraging results. However, further development is necessary to establish the correct indications, to determine the most-suited cell type, to standardize the cell preparation method and to validate the route and number of cell delivery. [ABSTRACT FROM AUTHOR]

Stress urinary incontinence (SUI) is a significant health concern for patients affected, impacting their quality of life severely. To investigate mechanisms contributing to SUI different animal models were developed. Incontinence was induced under defined conditions to explore the pathomechanisms involved, spontaneous recovery, or efficacy of therapies over time. The animal models were coined to mimic known SUI risk factors such as childbirth or surgical injury. However, animal models neither reflect the human situation completely nor the multiple mechanisms that ultimately contribute to the pathogenesis of SUI. In the past, most SUI animal studies took advantage of rodents or rabbits. Recent models present for instance transgenic rats developing severe obesity, to investigate metabolic interrelations between the disorder and incontinence. Using recombinant gene technologies, such as transgenic, gene knock-out or CRISPR-Cas animals may narrow the gap between the model and the clinical situation of patients. However, to investigate surgical regimens or cell therapies to improve or even cure SUI, large animal models such as pig, goat, dog and others provide several advantages. Among them, standard surgical instruments can be employed for minimally invasive transurethral diagnoses and therapies. We, therefore, focus in this review on large animal models of SUI. [ABSTRACT FROM AUTHOR]

Urinary incontinence (UI) is a major problem in health care and more than 400 million people worldwide suffer from involuntary loss of urine. With an increase in the aging population, UI is likely to become even more prominent over the next decades and the economic burden is substantial. Among the different subtypes of UI, stress urinary incontinence (SUI) is the most prevalent and focus of this review. The main underlying causes for SUI are pregnancy and childbirth, accidents with direct trauma to the pelvis or medical treatments that affect the pelvic floor, such as surgery or irradiation. Conservative approaches for the treatment of SUI are pelvic physiotherapy, behavioral and lifestyle changes, and the use of pessaries. Current surgical treatment options include slings, colposuspensions, bulking agents and artificial urinary sphincters. These treatments have limitations with effectiveness and bear the risk of long-term side effects. Furthermore, surgical options do not treat the underlying pathophysiological causes of SUI. Thus, there is an urgent need for alternative treatments, which are effective, minimally invasive and have only a limited risk for adverse effects. Regenerative medicine is an emerging field, focusing on the repair, replacement or regeneration of human tissues and organs using precursor cells and their components. This article critically reviews recent advances in the therapeutic strategies for the management of SUI and outlines future possibilities and challenges. [ABSTRACT FROM AUTHOR]

Erectile dysfunction (ED) has been defined as the inability to attain or maintain penile erection sufficient for successful sexual intercourse. ED carries a notable influence on life quality, with significant implications for family and social relationships. Because atherosclerosis of penile arteries represents one of the most frequent ED causes, patients presenting with it should always be investigated for potential coexistent coronary or peripheral disease. Up to 75% of ED patients have a stenosis of the iliac-pudendal-penile arteries, supplying the male genital organ's perfusion. Recently, pathophysiology and molecular basis of male erection have been elucidated, giving the ground to pharmacological and mechanical revascularization treatment of this condition. This review will focus on the normal anatomy and physiology of erection, the pathophysiology of ED, the relation between ED and cardiovascular diseases, and, lastly, on the molecular basis of erectile dysfunction. [ABSTRACT FROM AUTHOR]

During tissue injury events, the innate immune system responds immediately to alarms sent from the injured cells, and the adaptive immune system subsequently joins in the inflammatory reaction. The control mechanism of each immune reaction relies on the orchestration of different types of T cells and the activators, antigen-presenting cells, co-stimulatory molecules, and cytokines. Mitochondria are an intracellular signaling organelle and energy plant, which supply the energy requirement of the immune system and maintain the system activation with the production of reactive oxygen species (ROS). Extracellular mitochondria can elicit regenerative effects or serve as an activator of the immune cells to eliminate the damaged cells. Recent clarification of the cytosolic escape of mitochondrial DNA triggering innate immunity underscores the pivotal role of mitochondria in inflammation-related diseases. Human mesenchymal stem cells could transfer mitochondria through nanotubular structures to defective mitochondrial DNA cells. In recent years, mitochondrial therapy has shown promise in treating heart ischemic events, Parkinson's disease, and fulminating hepatitis. Taken together, these results emphasize the emerging role of mitochondria in immune-cell-mediated tissue regeneration and ageing. [ABSTRACT FROM AUTHOR]

Mitochondria are essential cellular components that ensure physiological metabolic functions. They provide energy in the form of adenosine triphosphate (ATP) through the electron transport chain (ETC). They also constitute a metabolic hub in which metabolites are used and processed, notably through the tricarboxylic acid (TCA) cycle. These newly generated metabolites have the capacity to feed other cellular metabolic pathways; modify cellular functions; and, ultimately, generate specific phenotypes. Mitochondria also provide intracellular signaling cues through reactive oxygen species (ROS) production. As expected with such a central cellular role, mitochondrial dysfunctions have been linked to many different diseases. The origins of some of these diseases could be pinpointed to specific mutations in both mitochondrial- and nuclear-encoded genes. In addition to their impressive intracellular tasks, mitochondria also provide intercellular signaling as they can be exchanged between cells, with resulting effects ranging from repair of damaged cells to strengthened progression and chemo-resistance of cancer cells. Several therapeutic options can now be envisioned to rescue mitochondria-defective cells. They include gene therapy for both mitochondrial and nuclear defective genes. Transferring exogenous mitochondria to target cells is also a whole new area of investigation. Finally, supplementing targeted metabolites, possibly through microbiota transplantation, appears as another therapeutic approach full of promises. [ABSTRACT FROM AUTHOR]

Although molecular mechanisms driving tumor progression have been extensively studied, the biological nature of the various populations of circulating tumor cells (CTCs) within the blood is still not well understood. Tumor cell fusion with immune cells is a longstanding hypothesis that has caught more attention in recent times. Specifically, fusion of tumor cells with macrophages might lead to the development of metastasis by acquiring features such as genetic and epigenetic heterogeneity, chemotherapeutic resistance, and immune tolerance. In addition to the traditional FDA-approved definition of a CTC (CD45-, EpCAM+, cytokeratins 8+, 18+ or 19+, with a DAPI+ nucleus), an additional circulating cell population has been identified as being potential fusions cells, characterized by distinct, large, polymorphonuclear cancer-associated cells with a dual epithelial and macrophage/myeloid phenotype. Artificial fusion of tumor cells with macrophages leads to migratory, invasive, and metastatic phenotypes. Further studies might investigate whether these have a potential impact on the immune response towards the cancer. In this review, the background, evidence, and potential relevance of tumor cell fusions with macrophages is discussed, along with the potential role of intercellular connections in their formation. Such fusion cells could be a key component in cancer metastasis, and therefore, evolve as a diagnostic and therapeutic target in cancer precision medicine. [ABSTRACT FROM AUTHOR]

Contemporary treatment algorithms for erectile dysfunction (ED) involve the use of medical therapies such as phosphodiesterase type 5 (PDE5) inhibitors and intracavernosal injection therapy of vasoactive agents, as well as vacuum erection devices and penile prosthesis implants in medically refractory cases. However, the current therapeutic options only address the symptoms of ED and not the underlying pathogenesis that results in ED. Newer and novel ED therapies aspire to reverse ED conditions by preventing cavernosal fibrosis, promoting endothelial revascularization and modulating various neuro-hormonal pathways. Regenerative therapeutic strategies such as low-intensity shock wave, gene and cellular-based therapies, and penile transplants are designed to improve penile hemodynamics and revitalize the cavernosal smooth muscle to mitigate and/or reverse underlying ED. This state-of-art article evaluates current and emerging therapeutic options for ED. [ABSTRACT FROM AUTHOR]

Ischemic stroke is associated with a tremendous economic and societal burden, and only a few therapies are currently available for the treatment of this devastating disease. The main therapeutic approaches used nowadays for the treatment of ischemic brain injury aim to achieve reperfusion, neuroprotection and neurorecovery. Therapeutic angiogenesis also seems to represent a promising tool to improve the prognosis of cerebral ischemia. This review aims to present the modern concepts and the current status of regenerative therapy for ischemic stroke and discuss the main results of major clinical trials addressing the effectiveness of stem cell therapy for achieving neuroregeneration in ischemic stroke. At the same time, as a glimpse into the future, this article describes modern concepts for stroke prevention, such as the implantation of bioprinted scaffolds seeded with stem cells, whose 3D geometry is customized according to carotid shear stress. [ABSTRACT FROM AUTHOR]

Catheter-related bladder discomfort (CRBD) is one of the most difficult symptoms during the postoperative period. Nefopam is a non-narcotic analgesic agent, which also has anticholinergic action. This study was performed to evaluate the effects of nefopam on CRBD in male patients undergoing robotic nephrectomy. A total of 109 male patients were randomly divided into two groups: the control group (n = 55) received 20 mL of normal saline, and the nefopam group (n = 54) received 20 mg of nefopam 1 h before the end of the operation. At postoperative times of 20 min, 1 h, 2 h, and 6 h, the severity of CRBD was measured using an 11-point numeric rating scale, respectively. The severity of CRBD in the nefopam group was significantly lower than that in the control group at 20 min (4.8 ± 1.3 vs. 2.3 ± 1.0, respectively, p = 0.012) and at 1, 2, and 6 h (3.5 ± 1.2, 2.7 ± 0.9, and 2.5 ± 1.0 vs. 4.1 ± 0.8, 1.6 ± 0.8, and 1.3 ± 0.6, respectively, p < 0001). Intraoperative nefopam administration reduced the severity of CRBD in patients undergoing robotic nephrectomy. [ABSTRACT FROM AUTHOR]

Effective therapies for erectile dysfunction (ED) associated with diabetes mellitus (DM) are needed. In this study, the effects of stromal cell-derived factor-1 (SDF-1)-expressing engineered mesenchymal stem cells (SDF-1 eMSCs) and the relevant mechanisms in the corpus cavernosum of a streptozotocin (STZ)-induced DM ED rat model were evaluated. In a randomized controlled trial, Sprague–Dawley (SD) rats (n = 48) were divided into four groups (n = 12/group): Normal (control), DM ED (diabetes induced by STZ), DM ED + BM-MSC (treated with bone marrow [BM]-derived MSCs), and DM ED + SDF-1 eMSC (treated with SDF-1-expressing BM-MSCs). After four weeks, intracavernosal pressure (ICP), an indicator of erectile function, was 0.75 ± 0.07 in the normal group, 0.27 ± 0.08 in the DM ED group, 0.42 ± 0.11 in the DM ED + BM-MSC group, and 0.58 ± 0.11 in the DM ED + SDF-1 eMSC group. BM-MSCs, especially SDF-1 eMSCs, improved ED (p < 0.05). SDF-1 eMSC treatment improved the smooth muscle content in the corpus cavernosum (p < 0.05). As SDF-1 expression increased, ED recovery improved. In the SDF-1 eMSC group, levels of neuronal nitric oxide synthase (nNOS) and phosphorylated endothelial NOS (p-eNOS) were higher than those in other groups (p < 0.05). In addition, high stromal cell-derived factor-1 (SDF-1) expression was associated with increased vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in DM ED rats (p < 0.05). Higher levels of phosphorylated protein kinase B (p-AKT)/protein kinase B (AKT) (p < 0.05) and B-cell lymphoma-2 (Bcl-2) and lower levels of the apoptosis factors Bcl2-associated x (Bax) and caspase-3 were observed in the MSC-treated group than in the DM ED group (p < 0.05). SDF-1 eMSCs showed beneficial effects on recovery from erectile function. [ABSTRACT FROM AUTHOR]

Stroke remains a major cause of death and disability in the United States and around the world. Solid safety and efficacy profiles of novel stroke therapeutics have been generated in the laboratory, but most failed in clinical trials. Investigations into the pathology and treatment of the disease remain a key research endeavor in advancing scientific understanding and clinical applications. In particular, cell-based regenerative medicine, specifically stem cell transplantation, may hold promise as a stroke therapy, because grafted cells and their components may recapitulate the growth and function of the neurovascular unit, which arguably represents the alpha and omega of stroke brain pathology and recovery. Recent evidence has implicated mitochondria, organelles with a central role in energy metabolism and stress response, in stroke progression. Recognizing that stem cells offer a source of healthy mitochondria—one that is potentially transferrable into ischemic cells—may provide a new therapeutic tool. To this end, deciphering cellular and molecular processes underlying dysfunctional mitochondria may reveal innovative strategies for stroke therapy. Here, we review recent studies capturing the intimate participation of mitochondrial impairment in stroke pathology, and showcase promising methods of healthy mitochondria transfer into ischemic cells to critically evaluate the potential of mitochondria-based stem cell therapy for stroke patients. [ABSTRACT FROM AUTHOR]