Balint Farkas

ABSTRACT PROBLEM: Pre-eclampsia is a common obstetrical disorder of placental origin with both local and systemic anomalies, which affects 3-5% of pregnancies representing the leading cause of maternal, fetal and neonatal mortality. Altough it is manifested in the second half of pregnancy, pre-eclampsia is thought to be an implantation disorder. The current hypothesis regarding the etiology of pre-eclampsia is focused on inadequate trophoblast invasion and placentation presumably as a result of maladaptation of maternal immune responses locally. Later on, an excessive maternal inflammatory response develops systemically in response to the placental factors released by the oxidatively stressed and functional impared placenta. TIM family is a relatively newly described group of molecules with a conserved structure and important immunological functions. A growing body of evidence supports the critical role of different TIM molecules as modulators of the immune response in transplant tolerance. There is mounting evidence that TIM-3 is a potent regulator of both the adaptive and innate immune response. TIM-3 is expressed in a variety of immune cells, including Th1, Th17, NK cells, NKT cells, regulatory T cells, dendritic cells, monocytes, macrophages and mast cells. Identification of Galectin-9 (Gal-9) as a ligand for TIM-3 has established the Galectin-9/TIM-3 pathway as an important regulator of Th1 immunity and tolerance induction. Although data about the role of Galectin-9/TIM-3 pathway in the pathogenesis of human diseases is emerging, data about their role during human pregnancy and feto-maternal immunological relationship is scarce. The aim of our present study was to investigate the expression of Galectin-9 and TIM-3 molecules by peripheral blood mononuclear cells in healthy pregnancy and pre-eclampsia. METHODS: Pregnant women with early onset pre-eclampsia and classical symptoms (hypertonia, proteinuria and edema) were included in the study. Healthy pregnant women appropriatelymatched for gestational age formed the control group. Peripheral bloodmononuclear cells (PBMC) were separated fromheparinized venous blood on Ficoll-Paque gradient. Separated PBMC were used for staining and flow cytometric analysis. RESULTS: Investigating peripheral blood lymphocytes of women with pre-eclampsia, our results showed a decreased TIM-3 expression by CD8+ T and NK cells compared to healthy pregnant women. Although Gal-9 expression by CD8+ T and NK cells was significantly higher in patients with pre-eclampsia, we hypothesize that low TIM-3 expression allows cells to escape Gal-9 induced cell death leading to uninhibited expansion of pro-inflammatory Th1 and Th17 responses characteristics of the maternal syndrome of the disease. CONCLUSIONS: These data suggest that Gal-9/TIM-3 pathway could play an important role in the immunoregulation during pregnancy and the altered Galectin-9 and TIM-3 expression could result in an enhanced systemic inflammatory response including the activation of Th1 lymphocytes and type-1 bias in pre-eclampsia. Understanding the pathways and molecules responsible for regulation of TIM-3 and Gal-9 expression will greatly facilitate the ability to ultimately modulate this pathway for therapeutic benefit. Since Gal-9/TIM-3 pathway play an important role in the induction of immunological tolerance, activation of the pathway might represent a novel therapeutic strategy for the treatment of pathological conditions during pregnancy

Introduction: female urethral diverticulum is an uncommon pathologic condition, with symptoms ranging from pain, dyspareunia to variable urinary symptoms. Our aim was the summarize the diagnosis and the treatment options of urethral diverticulum. Methods: a systematic review was carried out utilizing the publicly available medical databases, by using the keywords listed below. Results: medical history by a physical examination and augmented by voiding cystourethrography, positive pressure urethrography, endovaginal sonography, or magnetic resonance imaging remains the cornerstone of the diagnosis. In symptomatic patients surgical solution is required, including endovaginal diverticulectomy, or marsupialization which are the best choice for treatment. Conclusion: female UD has patients are usually candidates for operative treatment, although the currently available operative approaches have a relative high recurrence rate.

Introduction and hypothesis: Although several surgical techniques are aimed to stabilize the lost integrity at DeLancey Level II, none of them seemed to be optimal. Despite vaginal surgical approaches utilizing synthetic meshes has been well established, and widely debated, our aim was to establish an optimal surgical procedure to decrease the size of the implanted vaginal grafts. Methods: In a prospective preliminary study, 43 patients with lateral cystoceles were enrolled, and have been implanted a partially absorbable polypropylene/polyglycholic acid vaginal tape. The two endpoints of the tapes were administered above the ATFP, providing lateral support. In 53 % of the cases (23/43) the patients also received a TVT, due to co-existing SUI. Follow up examination were carried out six month after the operation. Results: We observed significant shift in the Aa points (-0.86 cm ± 0.56 SD to-2.95 cm ± 0.30 SD) and in the Ba points (-0.42 cm ± 0.59 SD to-2.65 cm ± 1.04 SD) pre and postoperatively. Those patients who had dual tape implanted 95% (22/23) were found to continent. During the six month follow up period no mesh extrusion, no dyspareunia and no recurrence were noted. Conclusions: The implantation of a vaginal tape is a relatively easily and quickly executed surgical technique, which is able to bypass laparoscopic approaches. The method can be combined with simultaneous TVT implantation in SUI patients. Although further studies with more participants, are required to assess the effectiveness of the approach.

Objective: Surgical techniques utilizing six arm synthetic meshes for apical prolapse repair has been established, and debated in the last few years. Such vaginal hysteropexy (HPX) has several advantages over abdominal or laparoscopic HPX, although even through transsacrospinous fixation the apical reinforcement is not perfect. Our aim was to achieve optimal apical support by multivectoral apical suspension with the use of eight arm polypropylene vaginal mesh. Methods: In a prospective preliminary study design, 29 patients with pelvic organ prolapse quantification (POP-Q) system stage II-IV anterior and central compartment prolapse were included. They underwent the implantation of an eight arm polypropylene mesh, through a single anterior vaginal incision. The fixation has been achieved through dual transobturator and dual apical (sacrospinous and sacrotuberal) sutureless anchoring. Results: we experienced significant improvement in the prolapse after surgery in all patients. The mean Aa point was ascended from 1.1 cm to-2.9 cm, consequently the mean Ba point changed from 2.5 cm to-2.9 cm, and the mean C point climbed from 0.6 cm to-7.5 cm after the surgery. All patients were subjectively satisfied after the intervention. During the 12 week follow up period no mesh extrusion and no dyspareunia were noted. Conclusions: the vaginal implantation of the eight arm mesh comes with high patient satisfaction rates, and achieves vertical vector stabilization of the vaginal apex through sacrotuberal fixation, although further studies with more participants are required to assess the effectiveness of the approach.

Background: Primary bladder neck obstruction is a rare clinical entity, reported to be responsible for 2.7-8% of lower urinary tract symptoms. It can lead to various urinary storage and voiding symptoms. The mainstay of treatment of female urethral strictures is urethral dilatation. Despite the long history of this method, it is unclear how far the female urethra should be dilated in correlation with residual urine volume. Case presentation: A 79-year-old Caucasian woman presented to our institute with urgency (12-15 times/day), nocturia (3 times/night), and reoccurring urinary tract infections. A physical examination revealed no anatomical malformation in her genital organs, 150 mL post-void urine retention, and a significant narrowing in the mid-segment of the urethra (4 mm). After informed consent, our patient underwent urethral dilatation ranging from Ch9 (3 mm) to Ch39 (13 mm), and reported no symptoms at the 4-week follow-up, with no post-void residual urine. Conclusions: The relatively low (around 50%) success rate of urethral dilatation might be improved by the utilization of wider dilatators, and the relaxation of the pubourethral ligament, achieved by a gentle downward saggital push during the intervention, although long-term studies with a large number of participants are necessary to prove our hypothesis.

Objective: Obesity is a growing worldwide epidemic, with increasing prevalence in both children and adults. Although several publications and books describe obesity as a major risk factor of pelvic organ prolapse (POP), we assumed that obesity might not be a predisposing factor of symptomatic stage II or higher POP. Methods: In a prospective cohort study, 1911 women suffering from symptomatic POP were included. Their data was compared to 1995 age, and parity matching women, with no prolapse as control, from January 2009 to December 2016. Obesity was determined by calculating the body mass index (BMI). Detailed medical history and standard demographic data were revealed, and analysed using multivariate analysis. Results: The average age was 56 years ± 13 SD (min: 22, max: 89), and the mean parity was 2.04 ± 0.95 SD per patient (min: 0, max: 13). The study population had average weight and height, resulting in a mean BMI of 26.69 ± 4.45 kg/m 2 compared to the control group BMI 26.85 ± 5.56 kg/m 2. Two third (66.6 %) of the study population were in postmenopause with an average BMI of 27.14 ± 4.31 kg/m 2 , while in premenopausal patients (33.4%) the BMI was found to be 25.78 ± 4.60 kg/m 2 respectively (p = 0.042). Multivariate analysis revealed no statistical significant difference between POP and control groups (p = 0.146). Conclusion: We emphasize that in our homogenous Caucasian Eastern-European population obesity might not act as a strong risk factor for symptomatic pelvic organ prolapse stage 2 or higher.

Introduction and hypothesis The Female Sexual Function Index (FSFI) has been used for clinical and research purposes in many countries. The aim of this study was to translate, adapt and perform a psychometric validation of a Hungarian version of the FSFI. Methods The FSFI was translated into Hungarian, and its precision was ascertained through reverse translation by an expert team. As a first step, 40 volunteers participated in an evaluation of the test-retest reliability of the Hungarian version over a 2week period. After that, 418 (331 control and 87 with pelvic organ prolapse) women who had been in a stable sexual relationship in the previous 4 weeks participated in the study. The data were summarized using descriptive statistics. The structure validity was examined by confirmatory factor analysis, with which we tested the hypothesized original factor structure, using maximum likelihood model estimation. We calculated the Comparative Fit Index (CFI), root mean square error of approximation (RMSEA), standardized root mean residual and Akaike information criterion (AIC). To test the internal consistency, Cronbach's alpha coefficients of the full scale were determined. Spearman's rank correlation was used for testing divergent validity and Mann-Whitney U-test for examining discriminant validity. Results The FSFI was easily understandable and acceptable as well as capable of adequately evaluating and measuring various aspects of female sexual functioning. A high degree of internal consistency was demonstrated by the Cronbach's alpha value (0.963). Conclusion The FSFI Hungarian version is a valid tool that measures the same functioning as the original English questionnaire.

Background: Ovarian hyperstimulation syndrome (OHSS) is a rare, yet severe, iatrogenic complication of ovulation induction therapy during assisted reproductive procedures. Our group previously detected atypical cells in the ascitic fluid of OHSS patients, although no malignancy developed during follow up. Here, the aim was to perform a comparative analysis of the cytokines present in the abdominal fluid of patients affected by OHSS versus patients with advanced ovarian cancer, a benign adnexal mass, or ovarian endometriosis. Methods: This prospective, non-randomized study was conducted at the Clinical Center of the

Background: Accumulating evidence are available on the involvement of l-arginine-nitric oxide (NO) system in complex biological processes and numerous clinical conditions. Particular attention was made to reveal the association of l-arginine and methylarginines to outcome measures of women undergoing in vitro fertilization (IVF). This review attempts to summarize the expression and function of the essential elements of this system with particular reference to the different stages of female reproduction. Methods: A literature search was performed on the PubMed and Google Scholar systems. Publications were selected for evaluation according to the results presented in the Abstract. Results: The regulatory role of NO during the period of folliculogenesis, oocyte maturation, fertilization, embryogenesis, implantation, placentation, pregnancy, and delivery was surveyed. The major aspects of cellular l-arginine uptake via cationic amino acid transporters (CATs), arginine catabolism by nitric oxide synthases (NOSs) to NO and l-citrulline and by arginase to ornithine, and polyamines are presented. The importance of NOS inhibition by methylated arginines and the redox-sensitive elements of the process of NO generation are also shown. Conclusion: The l-arginine-NO system plays a crucial role in all stages of female reproduction. Insufficiently low or excessively high rates of NO generation may have adverse influences on IVF outcome.

Introduction and hypothesis The aims of the study were the translation, cultural adaptation, and validation of self-administered Australian Pelvic Floor Questionnaire (APFQ) on a Hungarian population. Methods The validation was performed in 294 women over 18 who agreed to answer the Hungarian version of the APFQ. The validation of the questionnaire included evaluation of content/face validity, internal consistency, construct validity, test-retest reproducibility, discriminant validity and convergent validity. Results Acceptable and good internal consistency was observed in all four dimensions [McDonald's ω (95% confidence interval) coefficients were > 0.7 for each dimension: bladder 0.888, bowel 0.790, prolapse 0.895 and sexual function 0.738]. Test-retest analyses revealed high reproducibility with intraclass correlation coefficients (bladder 0.83, bowel 0.92, prolapse 0.96 and sexual function 0.87). Prolapse symptom score correlated significantly with Pelvic Organ Prolapse Quantification (POP-Q), and bladder score correlated significantly with the results of the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ UI SF) (convergent validity). Scores distinguished between patients with pelvic floor disorders and controls (high discriminant validity). Conclusions Hungarian version of the self-administered APFQ is a reliable and valid instrument for evaluating symptom severity and impact of pelvic floor dysfunction on the quality of life of Hungarian women.

Objective: Surgical techniques utilizing six arm synthetic meshes for apical prolapse repair has been established, and debated in the last few years. Such vaginal hysteropexy (HPX) has several advantages over abdominal or laparoscopic HPX, although even through transsacrospinous fixation the apical reinforcement is not perfect. Our aim was to achieve optimal apical support by multivectoral apical suspension with the use of eight arm polypropylene vaginal mesh. Methods: In a prospective preliminary study design, 29 patients with pelvic organ prolapse quantification (POP-Q) system stage II-IV anterior and central compartment prolapse were included. They underwent the implantation of an eight arm polypropylene mesh, through a single anterior vaginal incision. The fixation has been achieved through dual transobturator and dual apical (sacrospinous and sacrotuberal) sutureless anchoring. Results: we experienced significant improvement in the prolapse after surgery in all patients. The me...

Excessive sodium intake has been well established as a risk factor for the development and progression of cardiovascular and renal diseases. Its adverse effects are achieved by renal sodium retention and related volume expansion and by inducing low-grade inflammation and oxidative stress (OS) in the target tissues. This review presents the recent concept of nonosmotic sodium storage in the skin interstitium, the subsequent dissociation of sodium and volume homeostasis, and the cellular response to the increased tissue sodium concentration. Furthermore, data are shown on the sodium barrier and buffering potential of the endothelial glycocalyx that may protect the functional integrity of the endothelium when it is challenged by an increased sodium load. Finally, examples will be given of the involvement of oxygen free radicals (OFR) in sodium-induced tissue damage, and some clinical entities will be mentioned that are causally associated with sodium/volume retention and OS.

The most recent studies of progesterone research provide remarkable insights into the physiological role and clinical importance of this hormone. Although the name progesterone itself means “promoting gestation”, this steroid hormone is far more than a gestational agent. Progesterone is recognized as a key physiological component of not only the menstrual cycle and pregnancy but also as an essential steroidogenic precursor of other gonadal and non-gonadal hormones such as aldosterone, cortisol, estradiol, and testosterone. Based on current findings, progesterone and novel progesterone-based drugs have many important functions, including contraception, treatment of dysfunctional uterine bleeding, immune response, and prevention of cancer. Considering the above, reproduction and life are not possible without progesterone; thus, a better understanding of this essential molecule could enable safe and effective use of this hormone in many clinical conditions.

niques are aimed to stabilize the lost integrity at DeLancey Level II, none of them seemed to be optimal. Despite vaginal surgical approaches utilizing synthetic meshes has been well established, and widely debated, our aim was to establish an optimal surgical procedure to decrease the size of the implanted vaginal grafts. Methods: In a prospective preliminary study, 43 patients with lateral cystoceles were enrolled, and have been implanted a partially absorbable polypropylene/polyglycholic acid vaginal tape. The two endpoints of the tapes were administered above the ATFP, providing lateral support. In 53% of the cases (23/43) the patients also received a TVT, due to co-existing SUI. Follow up examination were carried out six month after the operation. Results: We observed significant shift in the Aa points (-0.86 cm ± 0.56 SD to -2.95 cm ± 0.30 SD) and in the Ba points (-0.42 cm ± 0.59 SD to -2.65 cm ± 1.04 SD) pre and postoperatively. Those patients who had dual tape implanted 95% (22/23) were found to continent. During the six month follow up period no mesh extrusion, no dyspareunia and no recurrence were noted. Conclusions: The implantation of a vaginal tape is a relatively easily and quickly executed surgical technique, which is able to bypass laparoscopic approaches. The method can be combined with simultaneous TVT implantation in SUI patients. Although further studies with more participants, are required to assess the effectiveness of the approach.

  Introduction and hypothesis Loss of anatomical support for the pelvic organs results in pelvic organ prolapse (POP). We hypothesized that daily self-management of a cube pessary might be a safe, feasible long-term treatment in women with symptomatic POP. Methods A cohort of 214 symptomatic POP patients (stage 2+) were enrolled prospectively (January to December 2015). Each patient was size-fitted with a space-filling cube pessary and completed a questionnaire online or by phone ≥5 years after her initial fitting. Change in quality of life (QoL) was measured with the Patient Global Impression of Improvement (PGI-I). Results Of 185 women included in our analyses, 174 (94%) were continuing to use their pessary 4 weeks post-insertion. Among those, 143 (82.2%) used the pessary successfully for ≥5 years. A large majority of these patients (88.8% [127 out of 143]) described their condition as much or very much improved compared with their pretreatment status (PGI–I). Adverse secondary ef...

Background: Gene products involved in reproduction frequently undergo post-transcriptional modifications by DNA methylation and histone acetylation. The aim was to assess the predictive value of gene expression levels of DNA methyltransferases (DNMTs) and histone deacetylases (HDACs) in patients treated with in vitro fertilization (IVF). In a prospective, l clinical study 31 consecutive patients with male (n=17) or female (n=14) infertility diagnoses were enrolled. Granulosa cells (GCs) and follicular fluid (FF) were obtained at the oocytes retrieval during IVF. mRNA levels of DNMT1, DNMT3a, DNMT3b and HDAC5, HDAC6 were measured in GCs and FF by quantitative RT-PCR using ROCHE Lightcycler 480. The outcome measures were the number of oocytes retrieved, mature oocytes and viable embryos, as well as chemical and clinical pregnancy.Results: It was demonstrated that genes for DNMTs and HDACs could be detected in nearly equal amount in GC and FF, however, only the DNMT3a transcript in FF ...

OBJECTIVE Prior studies demonstrated a positive association between increased genital hiatus (GH), advanced prolapse stage and levator ani muscle injury. Moreover wide GH is an established risk factor for recurrent pelvic organ prolapse (POP). Since excess vaginal space is not yet a dimension to estimate in Pelvic Organ Prolapse, we hypothesized that excess vaginal space has a positive correlation with increased GH and could be a new aspect for the assessment of the severity of POP and underlying pelvic muscle damage. We attempted to quantify excess vaginal space by different volumes of different cube pessary sizes. STUDY DESIGN In a prospective study, 716 symptomatic POP patients without any prior operations were enrolled from January 2011 to December 2017. All patients suffered from stage 2 POP or greater, where either the anterior, middle or posterior compartments or combinations of these were affected. As a conservative self-therapy, space-filling (Dr. Arabin®) cube pessaries were fitted. The size of each was individually adapted for each woman. For data analysis we used Spearman correlation test and Nonparametric statistical test. RESULTS All patients included in the study were asymptomatic one week after fitting the pessary. We revealed a positive significant correlation between the genital hiatus (GH) and the size of the cube pessary (ƍ = 0.777,p ≤ 0.001). We also found a positive significant correlation between the size of the cube pessaries and the POP-Q stage. We also managed to find significant differences between cube pessary sizes and corresponding GH values. CONCLUSIONS Cube pessary sizes may indicate the amount of excess vaginal space. Since excess vaginal space significantly correlates with the increase of the genital hiatus, it could be consider - as well as GH - as a marker for advanced prolapse stage, and a risk factor for the recurrence of pelvic organ prolapse.More studies are needed to identify factors related to excess vaginal space.

Introduction: The MHC (H-2d) and non-MHC genetic background make the BALB/c strain highly susceptible to inflammatory arthritis and spondylitis. Although different BALB/c colonies develop proteoglycan (PG)-induced arthritis (PGIA) and spondylitis (PGIS) in response to immunization with human cartilage PG, they show significant differences in disease penetrance, despite being maintained by the same vendor either at the same or different location. Methods: BALB/c female mice (24-26 weeks old after 4 weeks acclimatization), were immunized with a suboptimal dose of cartilage PG to explore even minute differences among 11 subcolonies purchased from five different vendors. Serum cytokines and (auto)antibodies, in vitro measured T cell responses were correlated with arthritis (and spondylitis) phenotypic scores. cDNA microarrays were also performed using spleen cells of naïve and immunized BALB/cJ and BALB/cByJ mice (both colonies from The Jackson Laboratories) which represent the two majo...

Objective: Obesity is a growing worldwide epidemic, with increasing prevalence in both children and adults. Although several publications and books describe obesity as a major risk factor of pelvic organ prolapse (POP), we assumed that obesity might not be a predisposing factor of symptomatic stage II or higher POP. Methods: In a prospective cohort study, 1911 women suffering from symptomatic POP were included. Their data was compared to 1995 age, and parity matching women, with no prolapse as control, from January 2009 to December 2016. Obesity was determined by calculating the body mass index (BMI). Detailed medical history and standard demographic data were revealed, and analysed using multivariate analysis. Results: The average age was 56 years ± 13 SD (min: 22, max: 89), and the mean parity was 2.04 ± 0.95 SD per patient (min: 0, max: 13). The study population had average weight and height, resulting in a mean BMI of 26.69 ± 4.45 kg/m2 compared to the control group BMI 26.85 ± ...

Background Ovarian hyperstimulation syndrome (OHSS) is a rare, yet severe, iatrogenic complication of ovulation induction therapy during assisted reproductive procedures. Our group previously detected atypical cells in the ascitic fluid of OHSS patients, although no malignancy developed during follow up. Here, the aim was to perform a comparative analysis of the cytokines present in the abdominal fluid of patients affected by OHSS versus patients with advanced ovarian cancer, a benign adnexal mass, or ovarian endometriosis. Methods This prospective, non-randomized study was conducted at the Clinical Center of the University of Pecs Department of Obstetrics and Gynecology/Reproductive Center between October 2016 and March 2018. Abdominal fluid samples were obtained from 76 patients and subjected to Luminex analysis. The samples were collected from patients with OHSS (OHSS; n = 16), advanced ovarian cancer (OC; n = 22), a benign adnexal mass (BAM; n = 21), or ovarian endometriosis (EM...

To examine the effect of furosemide on hypertension and edema in patients with pre-eclampsia experiencing high cardiac output. The present cohort study enrolled patients with pre-eclampsia who were admitted to the pregnancy pathology unit of the Department of Obstetrics and Gynecology, University of Pécs, Hungary, between January 1 and December 31, 2015. Eligible patients had singleton pregnancies with no fetal anomalies, high blood volume, visible edema, and a hematocrit concentration below 37 L/L. Blood pressure was measured and impedance cardiography was used to determine cardiac output for all patients before they received a 40-mg dose of furosemide; after 60 minutes blood pressure and cardiac output were measured again. The study enrolled 14 patients. Lower cardiac output (P=0.002), systolic blood pressure (P=0.002), and diastolic blood pressure (P=0.002) were recorded after furosemide administration, with patient heart rates remaining stable. The heart-rate stability suggests ...

There is little data in the literature regarding the feasibility and limitations of pessary therapy after pelvic reconstructive surgery for symptom recurrence for treating urinary incontinence. Hysterectomy is an important risk factor for failure of pessary fitting. We aimed to evaluate the influence of these prior surgeries on subsequent initial trials of fitting a pessary. Six hundred and twenty-nine women with symptomatic pelvic organ prolapse (POP) were included in a prospective cohort study from January 2014 to December 2015. All women had symptomatic stage ≥2 POP. During the study period, various types of pessaries were used for the fitting process. O the 629 women, 489 (77.7 %) had neither hysterectomy nor reconstructive pelvic surgery, and 24 (3.8 %) had hysterectomy for different indications. Initial pessary fitting was possible in all patients in both groups (100 %) 116 (18.4 %) had a total of 159 previous, predominantly vaginal, surgeries for POP, with or without vaginal hysterectomy. In 25/116 (21.5 %) cases, initial fitting was impossible due to altered anatomy. After one surgery, the probability of failure was 18.8 % (15/80) and after two 27.3 % (9/33). Of the three women who had three or more surgeries, one failure occurred. Surgery for POP is an important risk factor for an unsuccessful pessary fitting. It seems conclusive to recommend pessary treatment as a general first-line therapy for symptomatic POP, since after unsuccessful pessary treatment, women can still undergo surgery, whereas reversing treatment options might not always be feasible.

Until now, no valid Hungarian questionnaire has existed to evaluate the sexual quality of life of women with pelvic floor disorders. The aim of this study was to translate the Prolapse/Urinary Incontinence Sexual Questionnaire, IUGA-Revised (PISQ-IR), into Hungarian and to validate the translated PISQ-IR. PISQ-IR was translated and validated using three steps, as guided by the IUGA international protocol: forward translation by two urogynecologists, a community review process consisting of one-on-one cognitive interviews with 20 patients, and backward translation by a native English speaker. The final version was approved by the IUGA Working Group comprising the original authors. Among sexually active women, good internal consistency was observed for all scales of the adapted instrument: global quality (Cronbach's α = 0.75), condition impact (α = 0.87), desire (α = 0.82), arousal/orgasm (α = 0.67), partner-related (α = 0.61) and condition-specific (α = 0.67). Among women who were not sexually active, internal consistency was valid for three scales: condition-specific (α = 0.70), global quality (α = 0.81) and condition impact (α = 0.86). Cronbach's α could not be determined in the partner-related domain because only two items were included. Criterion validity and reliability showed strong significant correlations with the UI at the Clinical-Q values and the FSFI and PFDI-20 tests. The PISQ-IR Hungarian version is a valid and reliable tool that is equivalent to the original English questionnaire and assesses sexual function in Hungarian women with pelvic organ prolapse, urinary incontinence and/or fecal incontinence.

To determine whether proinflammatory cytokine treatment or the complete absence of select cytokines modulates the expression of RANKL and osteoprotegerin (OPG) in synovial fibroblasts. Fibroblasts were isolated from normal and rheumatoid human synovium and from normal or arthritic joints of wild-type and cytokine gene-deficient (interleukin-4-knockout [IL-4 (-/-)] and interferon-gamma-knockout [IFNgamma (-/-)]) mice. Fibroblasts were stimulated with proinflammatory cytokines (tumor necrosis factor alpha [TNFalpha], IL-1beta, and IL-17) or antiosteoclastogenic cytokines (IL-4 and IFNgamma), alone or in combination, and the expression of RANKL and OPG was measured. Proinflammatory cytokine-stimulated fibroblasts from rheumatoid and arthritic mouse joints expressed higher levels of RANKL and OPG than those from normal joints. IL-4 suppressed RANKL expression and increased OPG expression, IFNgamma reduced the production of both RANKL and OPG, and IL-17 had only a modest effect on the expression of RANKL or OPG. Additive effects of combination treatment (TNFalpha/IL-17 or IL-1beta/IL-17) were observed only in the human system. Extensive destruction was observed in the arthritic joints of IL-4 (-/-) mice, with a corresponding upward shift of the RANKL:OPG ratios. However, an IL-17 deficiency did not attenuate arthritis or reduce bone resorption. Proinflammatory cytokines induce the expression of RANKL and OPG in both human and murine synovial fibroblasts. The RANKL:OPG ratios are shifted in favor of bone protection by IL-4 treatment, and, to a lesser extent, by IFNgamma treatment. Unexpectedly, an IL-17 deficiency alone does not induce reduced inflammatory bone destruction. Our results suggest that synovial fibroblasts may significantly contribute to bone resorption through modulation of RANKL and OPG production in a cytokine-rich milieu of inflamed joints.

We provide general product formulas for the solutions of non-autonomous abstract Cauchy problems. The main technical tool is the application of evolution semigroup methods, allowing the direct application of existing results on autonomous problems. The results are then illustrated by the example of a imaginary time Schr\"odinger equation with time dependent potential. We also obtain convergence rates for the Strang-splitting applied to this problem.