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

L1R, A27L, A33R and B5R vaccinia virus genes expressed by fowlpox recombinants as putative novel orthopoxvirus vaccines

Background: The traditional smallpox vaccine, administered by scarification, was discontinued in the general population from 1980, because of the absence of new smallpox cases. However, the development of an effective prophylactic vaccine against smallpox is still necessary, to protect from the threat of deliberate release of the variola virus for bioterrorism and from new zoonotic infections, and to improve the safety of the traditional vaccine. Preventive vaccination still remains the most effective control and new vectors have been developed to generate recombinant vaccines against smallpox that induce the same immunogenicity as the traditional one. As protective antibodies are mainly directed against the surface proteins of the two infectious forms of vaccinia, the intracellular mature virions and the extracellular virions, combined proteins from these viral forms can be used to better elicit a complete and protective immunity. Methods: Four novel viral recombinants were constructed based on the fowlpox genetic background, which independently express the vaccinia virus L1 and A27 proteins present on the mature virions, and the A33 and B5 proteins present on the extracellular virions. The correct expression of the transgenes was determined by RT-PCR, Western blotting, and immunofluorescence. Results and Conclusions: Using immunoprecipitation and Western blotting, the ability of the proteins expressed by the four novel FPL1R, FPA27L, FPA33R and FPB5R recombinants to be recognized by VV-specific hyperimmune mouse sera was demonstrated. By neutralisation assays, recombinant virus particles released by infected chick embryo fibroblasts were shown not be recognised by hyperimmune sera. This thus demonstrates that the L1R, A27L, A33R and B5R gene products are not inserted into the new viral progeny. Fowlpox virus replicates only in avian species, but it is permissive for entry and transgene expression in mammalian cells, while being immunologically non\u2013cross-reactive with vaccinia virus. These recombinants might therefore represent safer and more promising immunogens that can circumvent neutralisation by vector-generated immunity in smallpox-vaccine-experienced humans

Prime-boost therapeutic vaccination in mice with DNA/DNA or DNA/Fowlpox virus recombinants expressing the Human Papilloma Virus type 16 E6 and E7 mutated proteins fused to the coat protein of Potato virus X

The therapeutic antitumor potency of a prime-boost vaccination strategy was explored, based on the mutated, nontransforming forms of the E6 (E6F47R) and E7 (E7GGG) oncogenes of Human Papilloma Virus type 16 (HPV16), fused to the Potato virus X (PVX) coat protein (CP) sequence. Previous data showed that CP fusion improves the immunogenicity of tumor-associated antigens and may thus increase their efficacy. After verifying the correct expression of E6F47RCP and E7GGGCP inserted into DNA and Fowlpox virus recombinants by Western blotting and immunofluorescence, their combined use was evaluated for therapy in a pre-clinical mouse model of HPV16-related tumorigenicity. Immunization protocols were applied using homologous (DNA/DNA) or heterologous (DNA/Fowlpox) prime-boost vaccine regimens. The humoral immune responses were determined by ELISA, and the therapeutic efficacy evaluated by the delay in tumor appearance and reduced tumor volume after inoculation of syngeneic TC-1* tumor cells. Homologous DNA/DNA genetic vaccines were able to better delay tumor appearance and inhibit tumor growth when DNAE6F47RCP and DNAE7GGGCP were administered in combination. However, the heterologous DNA/Fowlpox vaccination strategy was able to delay tumor appearance in a higher number of animals when E6F47RCP and in particular E7GGGCP were administered alone

Immobilisation of engineered molecules on electrodes and optical surfaces,

ABSTRACT Monolayers of genetically modified proteins with an hexahistidine tag, (His)6, were obtained by using a Ni -NTA chelator synthesized on gold sputtered surfaces (via sulphide bonds), or on gold and graphite (via sililating agents) working electrodes of screen-printed devices. Two kinds of proteins were produced and purified for this study: a) a recombinant antibody, derived from the 'single chain Fv' ( scFv) format; b) a photosystem II (PSII) core complex isolated from the mutant strain CP43-H of the thermophilic cyanobacterium Synechococcus elongatus. An scFv, previously isolated from a synthetic 'phage display' library, was further engineered with an alkaline phosphatase activity genetically added between the carbossi-terminal of the scFvs and the (His)6 to allow direct measurement of immobilisation. Renewable specific binding of (His)6-proteins to gold and graphite surfaces and fast and sensitive electrochemical or optical detection of analytes were obtained. Additionally, "on chip" protein preconcentration was conveniently achieved for biosensing purposes, starting from crude unpurified extracts and avoiding protein purification steps

Timing Analysis of the 2022 Outburst of the Accreting Millisecond X-Ray Pulsar SAX J1808.4-3658: Hints of an Orbital Shrinking

We present a pulse timing analysis of NICER observations of the accreting millisecond X-ray pulsar SAX J1808.4-3658 during the outburst that started on 2022 August 19. Similar to previous outbursts, after decaying from a peak luminosity of ≃1 × 1036 erg s-1 in about a week, the pulsar entered a ~1 month long reflaring stage. Comparison of the average pulsar spin frequency during the outburst with those previously measured confirmed the long-term spin derivative of ν˙SD=−(1.15±0.06)×10−15 Hz s-1, compatible with the spin-down torque of a ≈1026 G cm3 rotating magnetic dipole. For the first time in the last twenty years, the orbital phase evolution shows evidence for a decrease of the orbital period. The long-term behavior of the orbit is dominated by an ~11 s modulation of the orbital phase epoch consistent with a ~21 yr period. We discuss the observed evolution in terms of a coupling between the orbit and variations in the mass quadrupole of the companion star

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

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