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Background: Labial adhesions, a frequent gynecological condition in prepubertal girls, occur when the labia minora adhere along the midline. The prevailing hypothesis about their etiology suggests that labial adhesion may occur when the delicate and non-estrogenized labia minora undergo an inflammatory response, triggered by exposure to an irritant environment. Therefore, conservative treatment involves the application of topical estrogen or betamethasone cream. The role of androgens has not been considered yet in the pathophysiology or therapy of this condition. However, some studies have shown that androgen receptors are prevalent in the labia minora and vulvar vestibule. Case summary: We present the case of a 29-month-old girl with symptomatic labial adhesions. She was first ineffectively treated with topical estriol, and then she was treated with a galenic cream containing both estriol and testosterone with complete recovery and without side-effects. Conclusions: Both androgens and estrogens play a significant role in maintaining the physiological trophic state of the vulva and vagina, even during childhood. Topical estriol+testosterone could be considered an alternative treatment for prepubertal labial adhesions refractory to standard topical therapy.

Co-precipitation of biopolymers into calcium carbonate crystals changes their physicochemical and biological properties. This work studies hybrid microcrystals of vaterite obtained in the presence of natural polysaccharides, as carriers for the delivery of proteins and enzymes. Hybrid microcrystals with dextran sulfate, chondroitin sulfate, heparin, fucoidan, and pectin were obtained and compared. The impact of polysaccharides on the morphology (particle diameter, surface area, nanocrystallite and pore size), polysaccharide content and surface charge of hybrid microcrystals was studied. Only microcrystals with fucoidan and heparin exhibited antioxidant activity against •ОН radical. The surface charge and pore size of the hybrid microcrystals affected the sorption of albumin, catalase, chymotrypsin, mucin. A decrease in the catalytic constant and Michaelis constant was observed for catalase sorbed on the hybrid crystals. The biocompatibility of microcrystals depended on the nature of the included polysaccharide: crystals with sulfated polysaccharides increased blood plasma coagulation but not platelet aggregation, and crystals with dextran sulfate had the greatest cytotoxicity against HT-29 cells but not erythrocytes. Hybrid microcrystals with all polysaccharides except chondroitin sulfate reduced erythrocyte lysis in vitro compared with vaterite crystals. The obtained results enable to create novel carriers based on hybrid vaterite crystals with polysaccharides, beneficial for the delivery of protein drugs.

With the beginning of the special military operation (SMO), a new type of foreign trade policy is forming, based on restrictions. History shows that the practice of restrictions on trade operations is not new. The article compares Russia’s trade policy measures introduced during the First World War of 2014–2018 and the SMO, which began in 2022. The goal is to identify tools that are not currently used. Restrictions on exports and imports, measures to stimulate imports, and measures to build new trade routes are considered. Even before the start of the SMO, from the moment of political aggravation, Russia limited the export of wood and fertilizers, which contradicted the Protocol on Accession to the WTO and the refusal of quantitative restrictions. Unfriendly countries that applied preventive sanctions against Russia, with the beginning of the SMO, denied Russia most favored nation treatment. As during the First World War, grains, flour and sugar were among the food products subject to government export restrictions. Both periods were characterized by measures to stimulate imports in an effort to provide industry with raw materials and equipment. Import restriction measures in the first period applied to luxury goods, in the second they took the form of sanctions against unfriendly countries. The war period was characterized by growing interest in the northern sea routes. Compared with World War I, modern export restriction policies were more varied in terms of product coverage, but lacked the specific details by export directions that were developed a century ago. Many of the modern measures allow exemptions only in relation to EAEU countries. In our opinion, exemptions from restrictions on the export of humanitarian goods could be made for the developing countries which are most in need of grain or fertilizers.

Background: Vestibulodynia (VBD) represents a summation and overlapping of trigger factors (infections, hormonal disturbances, allergies, genetic aspects, psychological vulnerability, and others) with broad individual variability. As there are no standard treatment options for VBD, the disease is still in need of appropriate therapeutic tools. Objectives: A prospective observational trial was performed to confirm the efficacy of a topical gel containing a spermidine–hyaluronate complex (UBIGEL donna™) as either a stand-alone or companion treatment through a multicenter study on a large sample population. Methods: For women with VBD (n = 154), the treatment consisted of approximately two months (4 + 4 weeks) of applications according to the posology of UBIGEL. Evaluation of symptoms was performed on relevant clinical endpoints: dyspareunia and vulvovaginal pain/burning by a visual scale (VAS); vestibular trophism by a vestibular trophic health (VeTH) score; vulvoscopy through a cotton swab test; and the level of hypertonic pelvic floor by a physical graded assessment of levator ani hypertonus. Results: A total of 154 patients treated with UBIGEL donna™ showed significant improvements across all five evaluated parameters, including pain, dyspareunia, swab test results, muscle hypertonicity, and vestibular trophism. Pain and dyspareunia scores decreased by 46.5% and 33.5%, respectively, while significant improvements were also observed in the other parameters (p < 0.0001). These improvements were consistent across various stratifications, including age and disease duration. Conclusions: The findings of the present study suggest that UBIGEL donna™ is effective in alleviating pain and dyspareunia, as well as reducing vestibular hypersensitivity in women with VBD. Although UBIGEL donna™ alone cannot serve as a comprehensive substitute for all recommended therapies, we suggest that multimodal therapy strategies may be crucial for attaining substantial improvement in any aspect of the condition.

Objective Recurrent bacterial vaginosis (RBV) after antibiotic treatment has relapse rates of 35% within 3 months and 60% within 12 months. A medical device containing polycarbophil, lauryl glucoside, and glycerides (PLGG) inhibits bacterial growth and has mucoadhesive properties. This study examined the efficacy of the device in women with RBV. Methods This post-market clinical follow-up study comprised two phases. The first phase was an interventional, open-label, non-controlled, multicenter study enrolling 56 women. The second phase was an observational 10-month follow-up without treatment. Results After three cycles of PLGG treatment, recurrence was identified in 8 of 54 evaluable patients (14.81%). A positive effect on lactobacilli in the vaginal secretions was observed in 26 of 39 patients (66.67%). Among 35 patients observed after stopping PLGG treatment, one case of RBV (2.86%) was observed after 4 months, and an additional six cases (17.14%) were observed after 10 ± 2 months. Therefore, no recurrence was evidenced in 12 subjects (34.28%) at the end of the study. Conclusion The use of PLGG vaginal ovules in the treatment of BV reduces the rate of recurrence and apparently produces a positive effect on the vaginal microbiota.

BackgroundThe medical literature has reported that recurrent bacterial vaginosis (RBV) has a relapse rate of 35% within 3 months and 60% within 12 months after antibiotic administration. Products that are able to provide a barrier effect against the biofilm produced by Gardnerella vaginalis could play a role in improving the results of bacterial vaginosis (BV) treatment. ObjectiveThis study aims to assess the performance and safety of a medical device (Polybactum) containing polycarbophil, lauryl glucoside, and glycerides (PLGG) for reducing the rate of recurrence of BV. MethodsThe study includes women who are aged above 18 years, are willing to provide signed informed consent, have a diagnosis of BV according to the Amsel criteria, and have been affected by at least 2 episodes of RBV in the last 12 months. The trial includes 2 phases. In the first phase (according to an open-label noncontrolled design), the treatment involving PLGG is administered for 3 cycles and is followed by a 1-month period of follow-up without treatment. In the second phase, a 9-month follow-up period is envisaged. Thus, for each patient, a 10-month follow-up period without treatment is planned. The study involves 5 centers (2 in Italy and 3 in Romania). We calculated a sample size of 44 pairs to achieve a power of 80% and a 1-sided significance of 5% for detecting a difference of 0.25 between marginal proportions, in comparison with the mean recurrence rate of BV reported in the medical literature. We estimated a potential dropout rate of 20%, and thus, we decided to enroll 55 patients (1-group chi-square test). ResultsThe study received ethics approval in 2016 in Romania and 1 year later in Italy. Recruitment started in September 2016. An interim analysis was performed in 2019, and full study analysis results are expected in July 2023. ConclusionsThe tested medical device involving PLGG could modify the mechanisms involved in the pathogenesis of BV and could improve microbiological parameters owing to the acidifying effect on vaginal pH. We believe that the findings of our study could be useful for other investigators who want to test different products against RBV using a standardized protocol and standardized procedures. Trial RegistrationClinicalTrials.gov NCT02863536; https://clinicaltrials.gov/ct2/show/NCT02863536 International Registered Report Identifier (IRRID)RR1-10.2196/42787

Background and Objectives: Available evidence reports the overexpression of β1 integrin in dysplastic rather than normal cervical tissue. We aimed to evaluate the involvement of β1 (CD29) integrin in the progressive pathogenesis of cervical intraepithelial neoplasia (CIN). Materials and Methods: From January 2019 to December 2021, we prospectively enrolled women undergoing a colposcopy with a cervical biopsy for abnormal cervical cytology and/or undefined cytology with a positive HPV DNA test and women with relapsing cervical inflammatory disorders. Based on the histopathological results, women were divided into four groups: group A (CIN1), group B (CIN2), group C (CIN3), and group D (no CIN diagnosis) as a control group. Subsequently, cytofluorimetry and immunohistochemical analysis (based on the identified positive cell ratios as follows: ≤10%, negative; 10–25%, 1+ (weak); 25–50%, 2+ (medium); ≥50%, and 3+ (high)) for β1 integrin were carried out. Results: In total, 154 women were included. The average fluorescence intensity in the four groups was 2.35 ± 1.37, 2.73 ± 1.56, 3.09 ± 1.56, and 2.13 ± 1.25 UA from groups A to D, respectively; this figure was significantly different for CIN3 (group C) women relative to the other groups (p = 0.0132). Higher β1 integrin/CD29 concentrations in the CIN groups with HR-HPV 16 and 18 were also detected (p = 0.0292, 0.0367, and 0.0357 respectively for CIN3, CIN2, and CIN1). Immunohistochemistry analysis showed higher results for the CIN3 group compared to controls and all the other groups (p < 0.001). Conclusions: β1/CD29 integrin expression increased with CIN grade, and it was significantly higher in CIN3 lesions. This could be used as a promising screening tool to identify women prone to developing high-grade cervical lesions. However, additional evidence is needed to strengthen these findings.

PoxtA confers resistance to ribosome-targeting oxazolidinone (linezolid) and chloramphenicol antibiotics. Here, Crowe-McAuliffe et al. provide structural insights into how binding of PoxtA to the ribosome indirectly promotes drug dissociation.

Background: Vestibulodynia (VBD) represents a summation and overlapping of trigger factors (infections, hormonal disturbances, allergies, genetic aspects, psychological vulnerability, and others) with broad individual variability. As there are no standard treatment options for VBD, the disease is still in need of appropriate therapeutic tools. Objectives: A prospective observational trial was performed to confirm the efficacy of a topical gel containing a spermidine–hyaluronate complex (UBIGEL donna™) as either a stand-alone or companion treatment through a multicenter study on a large sample population. Methods: For women with VBD (n = 154), the treatment consisted of approximately two months (4 + 4 weeks) of applications according to the posology of UBIGEL. Evaluation of symptoms was performed on relevant clinical endpoints: dyspareunia and vulvovaginal pain/burning by a visual scale (VAS); vestibular trophism by a vestibular trophic health (VeTH) score; vulvoscopy through a cotton swab test; and the level of hypertonic pelvic floor by a physical graded assessment of levator ani hypertonus. Results: A total of 154 patients treated with UBIGEL donna™ showed significant improvements across all five evaluated parameters, including pain, dyspareunia, swab test results, muscle hypertonicity, and vestibular trophism. Pain and dyspareunia scores decreased by 46.5% and 33.5%, respectively, while significant improvements were also observed in the other parameters (p < 0.0001). These improvements were consistent across various stratifications, including age and disease duration. Conclusions: The findings of the present study suggest that UBIGEL donna™ is effective in alleviating pain and dyspareunia, as well as reducing vestibular hypersensitivity in women with VBD. Although UBIGEL donna™ alone cannot serve as a comprehensive substitute for all recommended therapies, we suggest that multimodal therapy strategies may be crucial for attaining substantial improvement in any aspect of the condition. [ABSTRACT FROM AUTHOR]

Background: Vestibulodynia (VBD) is the most common form of vulvodynia. Because VBD is a pain disorder, transcutaneous electrical nerve stimulation (TENS) can be used as treatment. This study aims to evaluate the effects of two-parameter combinations (frequency and pulse duration) of TENS in reducing pain intensity and dyspareunia in VBD. Methods: A randomized, double-blind, controlled trial was conducted to study the effect of two different electrical stimulation treatment regimens on women with VBD receiving domiciliary TENS. Outcomes were the mean change from baseline at 60 and 120 days of burning/pain and dyspareunia (VAS), Vulvar Pain Functional Questionnaire (V-Q), Female Sexual Functioning Index (FSFI) and vaginal electromyography measurements. Results: A total of 78 subjects, 39 in each group, completed the trial. Patients in Groups 1 and 2 received a mean of 46.9 and 48.4 TENS sessions. By day 120, there was a 38.2% reduction in the burning/pain and a 52.1% reduction in the dyspareunia VAS scores in Group 1, as compared to 21.3% (p = 0.003) and 23.1% in Group 2 (p = 0.01), respectively. FSFI, V-Q, and muscle-strength measures also improved but were not statistically significant. Conclusions: Our findings showed the potential of TENS in the treatment of VBD.

Mitochondrial ribosomes (mitoribosomes) are characterized by a distinct architecture and thus biogenesis pathway. Here, cryo-EM structures of mitoribosome large subunit assembly intermediates elucidate final steps of 16 S rRNA folding, methylation and peptidyl transferase centre (PTC) completion, as well as functions of several mitoribosome assembly factors.

Background: Labial adhesions, a frequent gynecological condition in prepubertal girls, occur when the labia minora adhere along the midline. The prevailing hypothesis about their etiology suggests that labial adhesion may occur when the delicate and non-estrogenized labia minora undergo an inflammatory response, triggered by exposure to an irritant environment. Therefore, conservative treatment involves the application of topical estrogen or betamethasone cream. The role of androgens has not been considered yet in the pathophysiology or therapy of this condition. However, some studies have shown that androgen receptors are prevalent in the labia minora and vulvar vestibule. Case summary: We present the case of a 29-month-old girl with symptomatic labial adhesions. She was first ineffectively treated with topical estriol, and then she was treated with a galenic cream containing both estriol and testosterone with complete recovery and without side-effects. Conclusions: Both androgens and estrogens play a significant role in maintaining the physiological trophic state of the vulva and vagina, even during childhood. Topical estriol+testosterone could be considered an alternative treatment for prepubertal labial adhesions refractory to standard topical therapy. [ABSTRACT FROM AUTHOR]

Introduction: The demand for effective and safe treatments of genitourinary syndrome (GSM) in post-menopausal women (PMW) is growing. Published data on the efficacy and safety of ospemifene (OSP) prompt an updated literature review to enlighten possible improvements in the GSM treatment. Area covered: We searched articles published in English from 2010 to 2023 through Medline (PubMed) and Embase databases with Boolean terms: OSP, PMW, GSM, endometrium, breast cancer, cardiometabolic syndrome, bone metabolism, adherence to treatment, and patient satisfaction. We selected randomized controlled trials (RCTs) and observational and cross-sectional studies and completed the search manually. Expert opinion: Of the 157 retrieved records, 25 primary studies met the inclusion criteria (15 regarding efficacy and safety, two for additional effects, and four for adherence and satisfaction with the OSP treatment). Seven RCTs involved nearly 5,000 patients, 10 out of 18 prospective observational studies 563, and six retrospective analyses 356,439. Evidence of OSP treatment in PMW with GSM relies on RCTs and remarkable real-world data. The 25 primary studies showcased the high clinical response to symptoms, the favorable safety profile of OSP with very few adverse events, a neutral impact on the endometrium, breast, bone, and thrombosis, and the possible improvement of cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

Background: Postmenopausal dyspareunia and vulvar pain are common complaints, affecting about 60% of women within a few years after hormone levels begin to decline (such as estrogen and androgen). Atrophic changes mainly located in the vulvar vestibule and vulnerability to vulvovaginal infections in postmenopause could be predisposing factors to the development of vulvar burning/pain and introital dyspareunia (vestibulodynia secondary to atrophy). Tibolone is the most effective and safe alternative for treating menopausal symptoms. The role of Lactobacilli and lactoferrin shows its effectiveness in the treatment of vaginal microbiota dysbiosis. The aim of the present study was to assess the efficacy of the combination of tibolone and an oral-specific Lactobacilli mixture in combination with bovine lactoferrin as synergistic therapy for the treatment of vestibulodynia related to atrophy. Methods: In this study, we included 35 postmenopausal women with at least 1 year of amenorrhea, affected by vulvar burning/pain and introital dyspareunia. All participants received treatment with open-label, oral Tibolone 2.5 mg and Lactobacilli mixture (5 × 109 CFU per capsule) in combination with bovine lactoferrin (Respecta®). Each product was taken once daily for 90 days. Results: After 90 d of therapy with TIB+ Respecta®, in 30 women that completed the treatment, there was a statistically significant decrease from the baseline in the mean of the Visual Analog Scale for vulvar burning/pain and a reduction in scores in the pain evaluation test. Conclusions: This study provides evidence that the combination of TIB+ Respecta® was effective in reducing symptoms related to vestibular pain and hypersensitivity in a postmenopausal setting. [ABSTRACT FROM AUTHOR]

Introduction: A multifactorial etiology has been implicated in the development and maintenance of vestibulodynia (VBD), and atrophic changes of the vestibular mucosa have been observed in many patients. Aim: To assess the vestibular mucosa thickness in patients with VBD by comparing this sample with a control group of healthy fertile women and postmenopausal patients with symptoms of genitourinary syndrome of menopause (GSM). Methods: Vestibular mucosa thickness was measured with a 20 MHz ultrasound probe (DermaScan C, Cortex Technology, Denmark), including both the epidermis and dermis. Main outcome measures: All women were evaluated by anamnesis, physical examination, and self-report symptoms. Thickness of the vestibular mucosa (expressed in micrometers) was determined by the B-mode, excluding the hyperechogenic entrance echo and hypoechogenic subcutis. Clinical data related to VBD and GSM were recorded using a 0- to 10-point visual analog scale related to dyspareunia and vulvar pain/burning (0 = no pain; 10 = worst possible pain). Results: A total of 85 patients were recruited: 24 with VBD, 20 with GSM-related symptoms, and 20 matched controls. Vestibular mucosa thickness measurements were not significantly different between the VBD (mean ± DS: 1,092.5 ± 226.1 μm) and GSM groups (1,059.7 ± 221.5 μm), while the parameter was significantly lower (P

Although oligomeric proteins are predominant in cells, their folding is poorly studied at present. This work is focused on the denaturant- and mutation-induced disassembly of the hexameric mutant Y55W of the Qβ host factor (Hfq) from mesophilic Pseudomonas aeruginosa (Pae). Using intrinsic tryptophan fluorescence, dynamic light scattering (DLS), and high-performance liquid chromatography (HPLC), we show that the dissociation of Hfq Y55W occurs either under the effect of GuHCl or during the pre-denaturing transition, when the protein concentration is decreased, with both events proceeding through the accumulation of stable intermediate states. With an extremely low pH of 1.4, a low ionic strength, and decreasing protein concentration, the accumulated trimers and dimers turn into monomers. Also, we report on the structural features of monomeric Hfq resulting from a triple mutation (D9A/V43R/Y55W) within the inter-subunit surface of the protein. This globular and rigidly packed monomer displays a high thermostability and an oligomer-like content of the secondary structure, although its urea resistance is much lower.

To appropriately switch between sessile and motile lifestyles, bacteria control expression of biofilm-associated genes through multiple regulatory elements. In Pseudomonas aeruginosa, the post-transcriptional regulator RsmA has been implicated in the control of various genes including those related to biofilms, but much of the evidence for these links is limited to transcriptomic and phenotypic studies. RsmA binds to target mRNAs to modulate translation by affecting ribosomal access and/or mRNA stability. Here, we trace a global regulatory role of RsmA to inhibition of the expression of Vfr—a transcription factor that inhibits transcriptional regulator FleQ. FleQ directly controls biofilm-associated genes that encode the PEL polysaccharide biosynthesis machinery. Furthermore, we show that RsmA alone cannot bind vfr mRNA but requires the assistance of RNA chaperone protein Hfq. This is the first example where a RsmA protein family member requires another protein for binding to its target RNA.

The (p)ppGpp-mediated stringent response is a bacterial stress response implicated in virulence and antibiotic tolerance. Both synthesis and degradation of the (p)ppGpp alarmone nucleotide are mediated by RelA-SpoT Homolog (RSH) enzymes which can be broadly divided in two classes: single-domain ‘short’ and multi-domain ‘long’ RSH. The regulatory ACT (Aspartokinase, Chorismate mutase and TyrA)/RRM (RNA Recognition Motif) domain is a near-universal C-terminal domain of long RSHs. Deletion of RRM in both monofunctional (synthesis-only) RelA as well as bifunctional (i.e., capable of both degrading and synthesizing the alarmone) Rel renders the long RSH cytotoxic due to overproduction of (p)ppGpp. To probe the molecular mechanism underlying this effect we characterized Escherichia coli RelA and Bacillus subtilis Rel RSHs lacking RRM. We demonstrate that, first, the cytotoxicity caused by the removal of RRM is counteracted by secondary mutations that disrupt the interaction of the RSH with the starved ribosomal complex – the ultimate inducer of (p)ppGpp production by RelA and Rel – and, second, that the hydrolytic activity of Rel is not abrogated in the truncated mutant. Therefore, we conclude that the overproduction of (p)ppGpp by RSHs lacking the RRM domain is not explained by a lack of auto-inhibition in the absence of RRM or/and a defect in (p)ppGpp hydrolysis. Instead, we argue that it is driven by misregulation of the RSH activation by the ribosome.