A systematic review and meta-analysis of the placebo effect on both semen quality and male infertility.

INTRODUCTION: Placebo influence on such objective indicators, as sperm quality and infertility, has not been studied previously, but some studies report that placebo may distort even objective outcomes. The aim of current study is to assess the placebo effect on fertility in patients suffering from sperm abnormalities and/or infertility. EVIDENCE ACQUISITION: We conducted a search of two databases (Scopus and MEDLINE) and identified placebo-controlled clinical trials which focused on sperm abnormalities and/or male infertility treatment. Primary outcomes included changes in semen parameters (volume, total count, sperm concentration in semen, progressive motility, morphology (normal cells)). Secondary outcomes included DNA fragmentation and change in pregnancy rate. EVIDENCE SYNTHESIS: Seventy-seven articles published from 1983 to 2022 were included. Statistically significant changes were observed for the following values: total sperm count, mean change 0.16 (95% CI 0.05, 0.26); P=0.004, I2=75.1%; and progressive motility, mean change 0.13 (95% CI 0.02, 0.24); P=0.026, I2=84.9%. In contrast, placebo did not affect sperm concentration, sperm volume, sperm morphology or DNA fragmentation index. The publication bias for all the values measured with Egger's test and funnel plots was low. CONCLUSIONS: The current meta-analysis indicated a statistically significant increase of total sperm count and progressive motility in the placebo group. In contrast, placebo did not affect sperm concentration, sperm volume, sperm morphology and DNA fragmentation index. These findings should be considered while planning or analyzing placebo-controlled clinical trials.

Contrast-enhanced ultrasound (CEUS) as a follow-up method after the focal treatment of renal tumors: systematic review and meta-analysis.

CONTEXT: Contrast-enhanced ultrasound (CEUS) is a cost-effective radiation-free diagnostic method that can be used for renal tumor postoperative visualization after ablative treatment. OBJECTIVE: To assess CEUS diagnostic accuracy comparing with CT and MRI as a follow-up method in short-term and long-term postoperative periods after renal tumor ablation. MATERIALS AND METHODS: A systematic review and meta-analysis were performed in Scopus and Medline databases using the query "(kidney OR rena* OR RCC) AND (ablation OR RFA OR MWA OR cryo*) AND CEUS". The endpoint of the study was the evaluation of the overall accuracy of CEUS. RESULTS: Twelve trials were included in the review. With CT or MRI as a reference, for a short-term group (< 6 weeks after ablation) pooled sensitivity was 90.2%, I2 = 0%; pooled specificity was 99.3%, I2 = 0%; pooled NPV was 98.6%, I2 = 0%; pooled PPV was 94.6%, I2 = 0%; the AUC on the SROC curve was 0.971. For the long-term group (> 6 weeks after ablation), pooled sensitivity was 95.3%, I2 = 0%; pooled specificity was 97.6%, I2 = 0%; PPV was 74.2%, I2 = 4%; NPV was 99.4%, I2 = 5%; AUC = 0.93. CONCLUSION: CEUS has high sensitivity and specificity in ruling out the presence of local recurrence after renal tumor ablation with a higher risk of false-positive results within follow-up > 6 weeks compared with that for CT or MRI. Further studies with a unified protocol and morphological control of local renal tumor recurrence after ablation are needed.

Role of monocarboxylate transporters and glucose transporters in prostate cancer.

OBJECTIVES: Currently, research of new diagnostic approaches to detect clinically significant prostate cancer is relevant because of the importance of early detection of aggressive forms of the disease, often challenging, even when using modern diagnostic tools. The aim of this review is to present the current knowledge regarding monocarboxylate transporters' and glucose transporters' expression as a component of glycolytic phenotype definition in prostate cancer cells. METHODS: We searched PubMed and Scopus databases. Twenty-six articles from 2003 to 2022 were included. Literature research and selection were carried out based on the recommendations of the PRISMA statement. RESULTS: The presence of "lactate shuttle" in the tumor tissue is associated with a worse prognosis. Increased expression of MCT2, MCT4, GLUT1, and down-regulation of GLUT3 are associated with prostate adenocarcinoma. MCT4 expression level correlates with the grade of tumor malignancy and disease prognosis. Up-regulation of GLUT1 and MCT4 is typical for hormone-resistant prostate cancer. Inhibition of MCT1 and MCT4 and GLUT1 in prostate cancer cells reduces their metabolic activity and growth rate, a suitable novel approach for targeted therapy. CONCLUSION: Review of the current studies showed that expression of certain MCTs and GLUTs types are associated with prostate cancer and some of them correlate with high malignancy and poor prognosis. Detection by immunohistochemistry of these transporters could represent a new diagnostic tool to identify aggressive forms of prostate cancer, and a novel therapeutic target for selective drugs.

In vitro renal calculi destruction by a high-frequency glow discharge plasma.

Despite the progress made in the treatment of nephrolithiasis, the existing methods of renal calculi destruction are not ideal and have both advantages and disadvantages. Considering the process of high-frequency glow discharge formation on the surface of an electrode and in an electrolyte solution, we obtained the results on the destruction of renal calculi in vitro. It was shown that the destruction of kidney stones by glow discharge plasma was caused by several processes-the plasma induced effect of hydrated electrons and shock wave effect of the electrolyte stimulated by electrical breakdowns in the plasma. The plasma generation modes were configured by estimating the thickness of the vapor-gas layer in which the plasma burns. Thus, the average rate of contact destruction of renal calculi was measured depending on the plasma generator input power and time of plasma exposure. We conclude that the method of stone fragmentation by high-frequency electrolyte plasma is rather perspective and can be used in endoscopic urology for percutaneous and transurethral lithotripsy.

Modeling Hepatotropic Viral Infections: Cells vs. Animals.

The lack of an appropriate platform for a better understanding of the molecular basis of hepatitis viruses and the absence of reliable models to identify novel therapeutic agents for a targeted treatment are the two major obstacles for launching efficient clinical protocols in different types of viral hepatitis. Viruses are obligate intracellular parasites, and the development of model systems for efficient viral replication is necessary for basic and applied studies. Viral hepatitis is a major health issue and a leading cause of morbidity and mortality. Despite the extensive efforts that have been made on fundamental and translational research, traditional models are not effective in representing this viral infection in a laboratory. In this review, we discuss in vitro cell-based models and in vivo animal models, with their strengths and weaknesses. In addition, the most important findings that have been retrieved from each model are described.

Terahertz radiation and the skin: a review.

SIGNIFICANCE: Terahertz (THz) radiation has demonstrated a great potential in biomedical applications over the past three decades, mainly due to its non-invasive and label-free nature. Among all biological specimens, skin tissue is an optimal sample for the application of THz-based methods because it allows for overcoming some intrinsic limitations of the technique, such as a small penetration depth (0.1 to 0.3 mm for the skin, on average). AIM: We summarize the modern research results achieved when THz technology was applied to the skin, considering applications in both imaging/detection and treatment/modulation of the skin constituents. APPROACH: We perform a review of literature and analyze the recent research achievements in THz applications for skin diagnosis and investigation. RESULTS: The reviewed results demonstrate the possibilities of THz spectroscopy and imaging, both pulsed and continuous, for diagnosis of skin melanoma and non-melanoma cancer, dysplasia, scars, and diabetic condition, mainly based on the analysis of THz optical properties. The possibility of modulating cell activity and treatment of various diseases by THz-wave exposure is shown as well. CONCLUSIONS: The rapid development of THz technologies and the obtained research results for skin tissue highlight the potential of THz waves as a research and therapeutic instrument. The perspectives on the use of THz radiation are related to both non-invasive diagnostics and stimulation and control of different processes in a living skin tissue for regeneration and cancer treatment.

Photocurable Methacrylate Derivatives of Polylactide: A Two-Stage Synthesis in Supercritical Carbon Dioxide and 3D Laser Structuring.

A two-stage polylactide modification was performed in the supercritical carbon dioxide medium using the urethane formation reaction. The modification resulted in the synthesis of polymerizable methacrylate derivatives of polylactide for application in the spatial 3D structuring by laser stereolithography. The use of the supercritical carbon dioxide medium allowed us to obtain for the first time polymerizable oligomer-polymer systems in the form of dry powders convenient for further application in the preparation of polymer compositions for photocuring. The photocuring of the modified polymers was performed by laser stereolithography and two-photon crosslinking. Using nanoindentation, we found that Young's modulus of the cured compositions corresponded to the standard characteristics of implants applied in regenerative medicine. As shown by thermogravimetric analysis, the degree of crosslinking and, hence, the local stiffness of scaffolds were determined by the amount of the crosslinking agent and the photocuring regime. No cytotoxicity was observed for the structures.

Fibrin-based Bioinks: New Tricks from an Old Dog.

For the past 10 years, the main efforts of most bioprinting research teams have focused on creating new bioink formulations, rather than inventing new printing set-up concepts. New tissue-specific bioinks with good printability, shape fidelity, and biocompatibility are based on "old" (well-known) biomaterials, particularly fibrin. While the interest in fibrin-based bioinks is constantly growing, it is essential to provide a framework of material's properties and trends. This review aims to describe the fibrin properties and application in three-dimensional bioprinting and provide a view on further development of fibrin-based bioinks.

Analysis of Learning Curve in Robot-Assisted Radical Prostatectomy Performed by a Surgeon.

This study aimed to report the learning curve in robot-assisted radical prostatectomy (RARP) performed by one surgeon who is experienced in laparoscopic prostatectomies. The records of 145 RARP cases performed between 2015 and 2017 were evaluated retrospectively. Patients were divided into three groups: group 1 comprised the first 49 cases, group 2 comprised 50-88 cases, and the rest of the cases were assigned to group 3. Continence was defined as the necessity to use at least one pad during a day. Additionally, erectile function recovery was defined as having erection sufficient for sexual intercourse regardless of using a phosphodiesterase type 5 inhibitor. Continence and erectile function recovery were assessed during interviews at 3, 6, and 12 months after surgery. First, all procedures were successfully performed without conversions or blood transfusions. The median follow-up period was 22 months. Moreover, the median skin-to-skin operative time (OT) was 220 minutes. The median blood loss was 150 ml, and the mean hospital stay was 8.9 ± 3.87 days. The median prostate volume was 36 cm³. The overall positive surgical margin rate was 13.1%. Overall, 38 (26.2%) postoperative complications were observed, and 17.9% of them were graded as minor. Anastomotic leakage decreased significantly from group 1 to group 3 (26.5% and 7%, respectively). The continence recovery (0-1 pad) rates were 60.6%, 75.7%, and 84.9% at 3, 6, and 12 months after surgery, respectively. Subsequently, the erectile function recovery rates were 50.9% and 65.4% at 6 and 12 months after surgery, respectively. In conclusion, there are several types of learning curves for RARP. First, the shallowest learning curve was observed for the OT. Regarding the analysis of "advanced learning curve," demonstrating the improvement of OT and blood loss is considered insufficient. Therefore, additional oncological and functional results that require a longer period of investigation are required.

Battling Neurodegenerative Diseases with Adeno-Associated Virus-Based Approaches.

Neurodegenerative diseases (NDDs) are most commonly found in adults and remain essentially incurable. Gene therapy using AAV vectors is a rapidly-growing field of experimental medicine that holds promise for the treatment of NDDs. To date, the delivery of a therapeutic gene into target cells via AAV represents a major obstacle in the field. Ideally, transgenes should be delivered into the target cells specifically and efficiently, while promiscuous or off-target gene delivery should be minimized to avoid toxicity. In the pursuit of an ideal vehicle for NDD gene therapy, a broad variety of vector systems have been explored. Here we specifically outline the advantages of adeno-associated virus (AAV)-based vector systems for NDD therapy application. In contrast to many reviews on NDDs that can be found in the literature, this review is rather focused on AAV vector selection and their preclinical testing in experimental and preclinical NDD models. Preclinical and in vitro data reveal the strong potential of AAV for NDD-related diagnostics and therapeutic strategies.

Skin tissue regeneration for burn injury.

The skin is the largest organ of the body, which meets the environment most directly. Thus, the skin is vulnerable to various damages, particularly burn injury. Skin wound healing is a serious interaction between cell types, cytokines, mediators, the neurovascular system, and matrix remodeling. Tissue regeneration technology remarkably enhances skin repair via re-epidermalization, epidermal-stromal cell interactions, angiogenesis, and inhabitation of hypertrophic scars and keloids. The success rates of skin healing for burn injuries have significantly increased with the use of various skin substitutes. In this review, we discuss skin replacement with cells, growth factors, scaffolds, or cell-seeded scaffolds for skin tissue reconstruction and also compare the high efficacy and cost-effectiveness of each therapy. We describe the essentials, achievements, and challenges of cell-based therapy in reducing scar formation and improving burn injury treatment.

Collagen fibrillar structures in vocal fold scarring and repair using stem cell therapy: a detailed histological, immunohistochemical and atomic force microscopy study.

Regenerative medicine opens new opportunities in the repair of cicatricial lesions of the vocal folds. Here, we present a thorough morphological study, with the focus on the collagen structures in the mucosa of the vocal folds, dedicated to the effects of stem cells on the vocal folds repair after cicatricial lesions. We used a conventional experimental model of a mature scar of the rabbit vocal folds, which was surgically excised with a simultaneous implantation of autologous bone marrow-derived mesenchymal stem cells (MSC) into the defect. The restoration of the vocal folds was studied 3 months postimplantation of stem cells and 6 months after the first surgery. The collagen structure assessment included histology, immunohistochemistry and atomic force microscopy (AFM) studies. According to the data of optical microscopy and AFM, as well as to immunohistochemical analysis, MSC implantation into the vocal fold defect leads not only to the general reduction of scarring, normal ratio of collagens type I and type III, but also to a more complete restoration of architecture and ultrastructure of collagen fibres in the mucosa, as compared to the control. The collagen structures in the scar tissue in the vocal folds with implanted MSC are more similar to those in the normal mucosa of the vocal folds than to those of the untreated scars. AFM has proven to be an instrumental technique in the assessment of the ultrastructure restoration in such studies. LAY DESCRIPTION: Regenerative medicine opens new opportunities in the repair of the vocal fold scars. Because collagen is a main component in the vocal fold mucosa responsible for the scar formation and repair, we focus on the collagen structures in the mucosa of the vocal folds, using a thorough morphological study based on histology and atomic force microscopy (AFM). Atomic force microscopy is a scanning microscopic technique which allows revealing the internal structure of a tissue with a resolution up to nanometres. We used a conventional experimental model of a mature scar of the rabbit vocal folds, surgically excised and treated with a mesenchymal stem cells transplant. Our morphological study, primarily AFM, explicitly shows that the collagen structures in the scarred vocal folds almost completely restore after the stem cell treatment. Thus, the modern microscopic methods, and especially AFM are instrumental tools for monitoring the repair of the vocal folds scars.

Author Correction: Optimization of Photosensitized Tryptophan Oxidation in the Presence of Dimegin-Polyvinylpyrrolidone-Chitosan Systems.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Surgical site infections after radical prostatectomy: A comparative study between robot-assisted laparoscopic radical prostatectomy and retropubic radical prostatectomy.

OBJECTIVE: Surgical site infection (SSI) is defined as infection at or near surgical incisions within 30 days of an operative procedure and classified either incisional superficial and deep or organ/space. The aim of the study is to report and compare the incidence and management of SSIs after robot-assisted laparoscopic radical prostatectomy (RALP) and retropubic radical prostatectomy (RRP). MATERIAL AND METHODS: Within the last 4 years, we identified 285 patients that underwent RRP, n=187 (66%) or RALP, n=98 (34%). We reviewed the frequency, types and way of management of SSI complications. RESULTS: A significant difference was found between RALP and RRP (2/98, 2% vs. 27/187, 14.4%; p<0.0001) as for SSIs. The time interval between the time of surgery and diagnosis of SSIs was longer in RALP relative to RRP (median 13.5 vs. 12.9 days, p=0.761). CONCLUSION: All types of SSIs could be developed after RP, however RALP patients only experienced organ or space SSIs and have a lower rate of SSIs and shorter treatment time.

Optimization of Photosensitized Tryptophan Oxidation in the Presence of Dimegin-Polyvinylpyrrolidone-Chitosan Systems.

By the example of a model process of tryptophan photooxidation in the aqueous medium in the presence of a three-component photosensitizing complex (porphyrin photosensitizer-polyvinylpyrrolidone- chitosan, PPS-PVP-CT) in the temperature range of 20-40 °Ð¡, we have demonstrated a possibility of modification of such a process by selecting different molar ratios of the components in the reaction mixture. The actual objective of this selection is the formation of a certain PPS-PVP-CT composition in which PVP macromolecules would coordinate with PPS molecules and at the same time practically block the complex binding of PPS molecules with chitosan macromolecules. Such blocking allows utilization of the bactericidal properties of chitosan to a greater extent, since chitosan is known to depress the PPS photosensitizing activity in PPS-PVP-CT complexes when using those in photodynamic therapy (PDT). The optimal composition of photosensitizing complexes appears to be dependent on the temperature at which the PDT sessions are performed. We have analyzed the correlations of the effective rate constants of tryptophan photooxidation with the photophysical characteristics of the formed complexes.