Use of intravesical injections of platelet-rich plasma for the treatment of bladder pain syndrome: A comprehensive literature review

Background: Bladder pain syndrome/interstitial cystitis (BPS/IC) or primary bladder pain syndrome (PBPS) is a complex and poorly understood condition. This comprehensive review aimed to discuss the potential application of platelet-rich plasma (PRP) in the treatment of BPS/IC. The pathophysiology of BPS/IC is characterized by urothelial damage that triggers a chain of events leading to chronic inflammation and other conditions. Frequently, in subjects affected by BPS/IC, recurrent urinary tract infection (rUTI) is associated with difficult therapeutic management. For these reasons, many oral and intravesical treatments (e.g., antibiotic therapy and intravesical anesthetic instillations) have been proposed to alleviate the symptoms of IC/BPS. However, the limitation of these treatments is the short duration of improvement. The purpose of this review is to analyze the efficacy of intravesical PRP injections in subjects with PBS/IC and to try to understand the potential therapeutic effects on the pathophysiology of this disease. Methods: A nonsystematic literature search using Pubmed, EMBASE, Scopus, Web of Science, Medline was performed from January 2000 to August 2021. The following terms were combined to capture relevant publications: “platelet-rich plasma”, “interstitial cystitis”, “PRP”, “bladder pain syndrome”, and “painful bladder syndrome”. Results: After exclusion of non-pertinent studies/articles, we have analyzed 5 studies. In detail, 2 articles concerned preclinical studies in which animal models were used. The authors showed an improvement in the histological pattern with less bleeding in treated subjects, a lower presence of inflammatory cytokines and an increase in the mitotic index of urothelial cells in animals treated with intravesical PRP. In the three prospective clinical trials analyzed, patients with BPS/IC who underwent monthly intravesical PRP injections were found to have a statistically significant improvement in symptoms with modulation of growth factors and inflammatory proteins. Conclusions: New evidence suggests that treatment with intravesical PRP could improve urothelial regeneration and reduces chronic inflammation in BPS/IC, modifying the clinical history of its pathology

Evolution of an insect immune barrier through horizontal gene transfer mediated by a parasitic wasp.

Genome sequencing data have recently demonstrated that eukaryote evolution has been remarkably influenced by the acquisition of a large number of genes by horizontal gene transfer (HGT) across different kingdoms. However, in depth-studies on the physiological traits conferred by these accidental DNA acquisitions are largely lacking. Here we elucidate the functional role of Sl gasmin, a gene of a symbiotic virus of a parasitic wasp that has been transferred to an ancestor of the moth species Spodoptera littoralis and domesticated. This gene is highly expressed in circulating immune cells (haemocytes) of larval stages, where its transcription is rapidly boosted by injection of microorganisms into the body cavity. RNAi silencing of Sl gasmin generates a phenotype characterized by a precocious suppression of phagocytic activity by haemocytes, which is rescued when these immune cells are incubated in plasma samples of control larvae, containing high levels of the encoded protein. Proteomic analysis demonstrates that the protein Sl gasmin is released by haemocytes into the haemolymph, where it opsonizes the invading bacteria to promote their phagocytosis, both in vitro and in vivo. Our results show that important physiological traits do not necessarily originate from evolution of pre-existing genes, but can be acquired by HGT events, through unique pathways of symbiotic evolution. These findings indicate that insects can paradoxically acquire selective advantages with the help of their natural enemies

Sexual and functional outcomes of prostate artery embolisation. A prospective long-term follow-up, large cohort study.

Among minimally invasive procedures for treating benign prostate hyperplasia (BPH) prostate artery embolisation (PAE) is described as safe and effective. Aim of this study is to report our results, focusing on sexual outcomes (erectile and ejaculatory functions sparing) of PAE in patients suffering from bladder outlet obstruction (BOO) secondary to BPH

Sexual function after pelic organ prolapse surgery. Trocarless Transvaginal Mesh (TTMS) vs. laparoscopic transperitoneal pelvic organ prolapse suspension

Stress urinary incontinence (SUI) and low urinary tract symptoms related to pelvic organs prolapse represent a common condition that negatively impacts on female sexuality (FS). The repair of this anatomical/functional condition could affect female sexual function. Laparoscopic approach known as “pelvic organ prolapse surgery” (POPs) or the anterior repair with a trocar-less trans-vaginal mesh (TTMs) represent two different surgical techniques to reach functional and sexual improvements. This study aimed to compare the results of minimally invasive approach (POPs) with open trans-vaginal mesh tape repair for the correction of SUI and to evaluate the different outcomes on sexual activity and urinary symptoms

A prime/boost strategy using DNA/fowlpox recombinants expressing the genetically attenuated E6 protein as a putative vaccine against HPV-16-associated cancers

Background: Considering the high number of new cases of cervical cancer each year that are caused by human papilloma viruses (HPVs), the development of an effective vaccine for prevention and therapy of HPV-associated cancers, and in particular against the high-risk HPV-16 genotype, remains a priority. Vaccines expressing the E6 and E7 proteins that are detectable in all HPV-positive pre-cancerous and cancer cells might support the treatment of HPV-related lesions and clear already established tumors. Methods: In this study, DNA and fowlpox virus recombinants expressing the E6F47R mutant of the HPV-16 E6 oncoprotein were generated, and their correct expression verified by RT-PCR, Western blotting and immunofluorescence. Immunization protocols were tested in a preventive or therapeutic pre-clinical mouse model of HPV-16 tumorigenicity using heterologous (DNA/FP) or homologous (DNA/DNA and FP/FP) prime/boost regimens. The immune responses and therapeutic efficacy were evaluated by ELISA, ELISPOT assays, and challenge with TC-1* cells. Results: In the preventive protocol, while an anti-E6-specific humoral response was just detectable, a specific CD8+ cytotoxic T-cell response was elicited in immunized mice. After the challenge, there was a delay in cancer appearance and a significant reduction of tumor volume in the two groups of E6-immunized mice, thus confirming the pivotal role of the CD8+ T-cell response in the control of tumor growth in the absence of E6-specific antibodies. In the therapeutic protocol, in-vivo experiments resulted in a higher number of tumor-free mice after the homologous DNA/DNA or heterologous DNA/FP immunization. Conclusions: These data establish a preliminary indication for the prevention and treatment of HPV-related tumors by the use of DNA and avipox constructs as safe and effective immunogens following a prime/boost strategy. The combined use of recombinants expressing both E6 and E7 proteins might improve the antitumor efficacy, and should represent an important approach to control HPV-associated cancers

The Impact of Lockdown on Couples' Sex Lives

Background: the aim of this study was to perform an Italian telematics survey analysis on the changes in couples' sex lives during the coronavirus disease 2019 (COVID-19) lockdown. Methods: a multicenter cross sectional study was conducted on people sexually active and in stable relationships for at least 6 months. To evaluate male and female sexual dysfunctions, we used the international index of erectile function (IIEF-15) and the female sexual function index (FSFI), respectively; marital quality and stability were evaluated by the marital adjustment test (items 10-15); to evaluate the severity of anxiety symptoms, we used the Hamilton Anxiety Rating Scale. The effects of the quarantine on couples' relationships was assessed with questions created in-house. Results: we included 2149 participants. The sex lives improved for 49% of participants, particularly those in cohabitation; for 29% it deteriorated, while for 22% of participants it did not change. Women who responded that their sex lives deteriorated had no sexual dysfunction, but they had anxiety, tension, fear, and insomnia. Contrarily, men who reported deteriorating sex lives had erectile dysfunctions and orgasmic disorders. In both genders, being unemployed or smart working, or having sons were risk factors for worsening the couples' sex lives. Conclusion: this study should encourage evaluation of the long-term effects of COVID-19 on the sex lives of couples

Production of functional, stable, unmutated recombinant human papillomavirus E6 oncoprotein: Implications for HPV-tumor diagnosis and therapy

Background: High-risk human papillomaviruses (HR-HPVs) types 16 and 18 are the main etiological agents of cervical cancer, with more than 550,000 new cases each year worldwide. HPVs are also associated with other ano-genital and head-and-neck tumors. The HR-HPV E6 and E7 oncoproteins are responsible for onset and maintenance of the cell transformation state, and they represent appropriate targets for development of diagnostic and therapeutic tools. Methods: The unmutated E6 gene from HPV16 and HPV18 and from low-risk HPV11 was cloned in a prokaryotic expression vector for expression of the Histidine-tagged E6 protein (His6-E6), according to a novel procedure. The structural properties were determined using circular dichroism and fluorescence spectroscopy. His6-E6 oncoprotein immunogenicity was assessed in a mouse model, and its functionality was determined using in vitro GST pull-down and protein degradation assays. Results: The His6-tagged E6 proteins from HPV16, HPV18, and HPV11 E6 genes, without any further modification in the amino-acid sequence, were produced in bacteria as soluble and stable molecules. Structural analyses of HPV16 His6-E6 suggests that it maintains correct folding and conformational properties. C57BL/6 mice immunized with HPV16 His6-E6 developed significant humoral immune responses. The E6 proteins from HPV16, HPV18, and HPV11 were purified according to a new procedure, and investigated for protein-protein interactions. HR-HPV His6-E6 bound p53, the PDZ1 motif from MAGI-1 proteins, the human discs large tumor suppressor, and the human ubiquitin ligase E6-associated protein, thus suggesting that it is biologically active. The purified HR-HPV E6 proteins also targeted the MAGI-3 and p53 proteins for degradation. Conclusions: This new procedure generates a stable, unmutated HPV16 E6 protein, which maintains the E6 properties in in vitro binding assays. This will be useful for basic studies, and for development of diagnostic kits and immunotherapies in preclinical mouse models of HPV-related tumorigenesis

Rosina - Rosetta Orbiter Spectrometer for Ion and Neutral Analysis

The Rosetta Orbiter Spectrometer for Ion and Neutral Analysis (ROSINA) will answer important questions posed by the mission's main objectives. After Giotto, this will be the first time the volatile part of a comet will be analyzed in situ. This is a very important investigation, as comets, in contrast to meteorites, have maintained most of the volatiles of the solar nebula. To accomplish the very demanding objectives through all the different phases of the comet's activity, ROSINA has unprecedented capabilities including very wide mass range (1 to >300 amu), very high mass resolution (m/Δ m > 3000, i.e. the ability to resolve CO from N2 and 13C from 12CH), very wide dynamic range and high sensitivity, as well as the ability to determine cometary gas velocities, and temperature. ROSINA consists of two mass spectrometers for neutrals and primary ions with complementary capabilities and a pressure sensor. To ensure that absolute gas densities can be determined, each mass spectrometer carries a reservoir of a calibrated gas mixture allowing in-flight calibration. Furthermore, identical flight-spares of all three sensors will serve for detailed analysis of all relevant parameters, in particular the sensitivities for complex organic molecules and their fragmentation patterns in our electron bombardment ion source