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Tobacco use is a major global health problem, contributing to premature death and disability. In Slovenia, the prevalence of smoking is higher than the EU average, emphasizing the need for effective tobacco control measures. The aim of this study was to identify the characteristics of patients most likely to benefit from pharmacotherapy for smoking cessation.

Abstract Background Progression of diabetic retinopathy occurs at least temporarily during pregnancy. Although the cause of this progression is not entirely understood, the immune phenomenon and chronic inflammation may play a significant role. During pregnancy in order to avoid fetus rejection, certain components of the immune system that are knowingly implicated in the pathogenesis of diabetic retinopathy are activated including generalized leukocyte activation and an increase in certain cytokine plasma levels. Activated leukocytes with up regulated adhesion molecules have an increased potential to bind to the endothelium cells of blood vessels. Leukocyte-endothelial interaction and the consequent leukostasis with capillary occlusion, ischemia and vascular leakage have a substantial role in the development of diabetic retinopathy. Furthermore, certain increased cytokines are known to cause blood-retinal-barrier breakdown whilst others promote angiogenic and fibrovascular proliferation and thereby can also be implicated in the pathogenesis of this diabetic complication. Presentation of the hypothesis We hypothesized that the activation of the immune system during gestation may have an influence on the course of retinopathy in pregnant diabetic women. Testing the hypothesis We suggest two prospective follow up studies conducted on women with type 1 diabetes mellitus. The first study would include a group of non-pregnant women and a group of diabetic women undergoing normal pregnancy matched for age and duration of diabetes. In the second study pregnant women would be divided into two groups: one with normal pregnancy and the other with preeclampsia. The procedure and data collection in both studies will be identical: a complete ophthalmological examination, glycaemic control, blood pressure measurement and venous blood samples for the determination of plasma levels of cytokines (TNF-alpha, IL-1beta, IL-6, IL-8) and adhesion molecules (ICAM-1, VCAM-1). Implications of the hypothesis Considering the present assumption, the gestational immune activation could be suggested as a potential risk factor for the development and progression of retinopathy in diabetic women. A better understanding of immunomodulatory effects of pregnancy on diabetic retinopathy pave the way for further investigations of the mechanism of its pathogenesis and could be essential for novel approaches to the treatment of this serious sight threatening complication of diabetes mellitus.

Aim: To determine Croatian healthcare (HC) professionals' perspectives on HC management and leadership challenges., Methods: This cross-sectional study, conducted between May and June 2021, enrolled 1179 respondents from both the public and private sector, including medical doctors, nurses, pharmacists, economists, and other HC professionals. Their perspective on various facets of HC management, namely governance, ownership, accountability, financing, and potential for improvement, were investigated using an anonymous online survey., Results: Most respondents agreed that the system may be allocating resources ineffectively and that political mandates unduly influenced management decisions, impeding accountability. Competencies in organizational and financial experience, along with communication and leadership skills, were deemed fundamental for health care managers. Participants overwhelmingly supported data-driven decision-making, improved education, and the development of leadership skills as key avenues for system enhancement., Conclusions: The study underscores the need for better financial management and overall governance, in the Croatian HC, offering insights that can inform evidence-based policy decisions and reforms toward a more efficient and accountable HC system.

Objectives: The purpose of this systematic review is to present and compare results from studies that have been using autologous tissue for POP repair., Methods: Systematic review was done according to the Cochrane Handbook for Systematic Reviews. We aimed to retrieve reports of published and ongoing studies on the efficacy and safety of autologous tissue in vaginal vault prolapse repair. The databases searched were MEDLINE (PubMed interface), Scopus, Cohrane Central Register of Controlled Trials (CENTRAL) and ClinicalTrials.gov., Results: The success rate varied among studies. In fascia-lata group success rate reports varied from 83 to a 100%, with a median follow-up from 12 to 52 months among studies. Rectus fascia reported success rates from 87 to a 100% with a follow-up of 12 months to longest of 98 months., Conclusion: Autologous tissues show satisfying outcomes in terms of safety and efficacy. Sacrocolpopexy procedure with fascia lata has better outcome in term of treatment of prolapse. Harvesting place on lateral side of buttock has more complications in comparison with rectus fascia but size of the graft can be wider in fascia-lata group., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: The COVID-19 pandemic forced many businesses to shift towards remote and hybrid working models. This study explored the association of the work-from-home model with employee satisfaction, work-life balance, and work-model preferences within MPlus Group, a leader in telework within the business process and technology outsourcing (BPTO) industry., Methods: We analyzed survey responses of 4,554 employees of MPlus Group across seven countries to assess the associations of working from home with job satisfaction, work-life balance, and preference regarding continuing to work from home., Results: Employees working within all models, and both women and men, reported high levels of job satisfaction and work-life balance, and most employees working from home expressed a desire to continue doing so., Discussion: Our findings suggest working from home does not lead to lower job satisfaction or work-life balance in the BPTO and similar industries. The study provides insights for organizations and policymakers navigating post-pandemic work dynamics. However, further research is needed to examine the long-term implications of remote work across diverse industries., Competing Interests: BK, DH, and TG are employees, SO is a shareholder of, and TO provides advising to MPlus Group. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Orešković, Milošević, Košir, Horvat, Glavaš, Sadarić, Knoop and Orešković.)

Background: The pandemic of COVID-19 had a profound impact on our community and healthcare system. This study aims to assess the impact of COVID-19 on psychiatric care in Croatia by comparing the number of acute psychiatric cases before coronavirus disease (2017-2019) and during the pandemic (2020-2022)., Materials and Methods: The paper is a retrospective, comparative analyzes of the hospital admission rate in Diagnosis Related Group (DRG) classes related to mental diseases, and organic mental disorders caused by alcohol and drug use. This study used DRG data from all acute hospitals in Croatia accredited to provide mental health care services and relevant publicly available data from the Croatian Institute of Public Health (CIPH) and the Croatian Health Insurance Fund (CHIF). All hospital admissions for acute psychiatric patients in Croatia were tracked during both periods under study., Results: During the pandemic, the average number of all such cases decreased by 28% in secondary and tertiary hospitals, and by 11% in specialist psychiatric hospitals. It was also found that during COVID-19, there was a decrease in case numbers in DRG classes related to major affective disorders and anxiety, alcohol, and drug intoxication (31, 48, 34 and 45%, respectively). However, the same period saw an increase in hospital activity for eating disorders and for involuntary admissions related to schizophrenia and paranoia (30, 34 and 39% respectively). There were no changes in the admission rate for cases related to opioid use., Conclusion: The COVID-19 pandemic resulted in both a steep decrease in the overall number of psychiatric cases inpatient treatment at mental health facilities and their DRG casemix. Increasing our understanding of how pandemics and isolation affect demand for psychiatric care will help us better plan for future crises and provide more targeted care to this vulnerable group., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kalanj, Ćurković, Peček, Orešković, Orbanić and Marshall.)

Background: DNA methylation, histone modifications, and miRNAs affect ovarian cancer (OC) progression and therapy response., Purpose: Identification of epigenetically downregulated miRNAs in drug-resistant OC cell lines with a possible role in drug resistance and/or drug-induced mesenchymal-like phenotype., Methods: MiRNA profiling was performed on parental and carboplatin-resistant OC cells, MES-OV and MES-OV CBP. RT-qPCR validation, epigenetic modulation and other CBP-resistant OC cell lines were used to select miRNAs of interest. The integration of miRNA-predicted target genes and differentially expressed genes (DEGs), pathway and functional analysis were used for forecasting their biological role. Data mining was performed to determine their possible prognostic and predictive values., Results: MiRNA profiling revealed 48 downregulated miRNAs in OC cells whose drug sensitivity and metastatic potential were impacted by epigenetic modulators. Of the fourteen selected, nine were validated as changed, and seven of these restored their expression upon treatment with epigenetic inhibitors. Only three had similar expression patterns in other OC cell lines. MiRNA-mRNA integrative analysis resulted in 56 target DEGs. Pathway analysis revealed that these genes are involved in cell adhesion, migration, and invasion. The functional analysis confirmed the role of miR-103a-3p, miR-17-5p and miR-107 in cell invasion, while data mining showed their prognostic and predictive values. Only miR-103a-3p was epigenetically regulated at the constitutive level., Conclusion: High throughput miRNA and cDNA profiling coupled with pathway analysis and data mining delivered evidence for miRNAs which can be epigenetically regulated in drug-resistant, mesenchymal-like OC cells as possible markers to combat therapy-induced short overall survival and tumor metastatic potential., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: The COVID-19 pandemic significantly affected our society and healthcare system. This study aims to evaluate the effects of COVID-19 on the number of hospitalized patients with dermatological diseases in Croatia, as well as the number of these patients treated surgically and conservatively, before (2017-2019) and during the pandemic (2020-2021)., Materials and Methods: This is a retrospective, comparative study of the hospital admission rate for patients with skin, subcutaneous tissue, and breast disorders both before and during the pandemic. This study used data from the Croatian Institute of Public Health (CIPH) and the Croatian Health Insurance Fund (CHIF). Inpatient data for the CHIF data collection were categorized using the Australian Refined Diagnosis Related Groups (AR-DRGs). All hospital admissions for dermatology patients at all non-specialized hospitals in Croatia were tracked during two periods, before (2017-2019) and during the pandemic (2020-2021)., Results: The average number of dermatology patients in all hospitals fell by 29% during the pandemic. The overall number of dermatological patients admitted to hospitals fell by 32% in 2020 and by 26% in 2021 when compared to the number of patients admitted each year on average over the preceding 3 years. Additionally, there was an average 22% fall in surgical procedures performed during the pandemic. The only exception for surgical procedures is Major Breast Reconstruction for which is noted an increase, as also for Malignant Breast Disorders, Minor Complexity and Major Skin Disorders, Minor Complexity in a group of non-surgically treated patients., Conclusion: Examining the all consequences of the Croatian dermatological patient care interruption will require more investigation. Reduced access to medical care during the pandemic is anticipated to lead to later illness diagnosis, a later start to treatment, a poorer disease prognosis, as well as higher medical expenditures., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kalanj, Orbanić, Peček, Orešković, Marshall and Šitum.)

Objectives: The provide a descriptive analysis of the available population-level aggregated data on committed suicides in the Republic of Croatia, in the 2004-2018 period, showing emerging trends in suicide incidence focusing on sex/age/geographical distribution of suicides and the primary and secondary causes of suicide mortality, as well as making comparisons with similar neighboring neighboring countries., Methods: The aggregated suicide data were obtained from the Croatian Committed Suicides Registry, a national registry maintained by the public health authority. The raw data extract was organized into tables according to several variables (age, sex, place of birth, place of residence, and cause of death). Simple descriptive statistics were performed on the structured data., Results: Despite being among the highest in the world and EU, the number of committed suicides in Croatia is in decline since 2004. A higher number of suicides by males was observed when compared to females. Most of the suicides occur during spring and summer. The wealthier, northern continental region of the country had the highest average rate of committed suicides per 1,00,000 population, contrary to some of the findings in the published literature associating economic instability with suicide. The most common way to commit suicide for both sexes in all age groups is self-harm by hanging, strangulation and suffocation. Suicide by firearm and explosive devices discharge remains higher than the global average., Conclusions: Despite its steadily declining incidence rates in the past 20 years, suicides remain a major public health challenge in Croatia. Results may bolster the Ugro-Finnish suicide hypothesis, linking higher suicide rates to regions with populations of Hungarian descent., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pajić and Orešković.)

Aim: To assess the impact of Croatian reforms related to the funding of inpatient care on the efficiency of acute hospitals., Methods: Between 2009 and 2018, the study analyzed resourcing, performance, and financing data for 33 acute hospitals. It used data from the Croatian Health Insurance Fund (CHIF) and the Croatian Institute of Public Health and included hospital activity and diagnosis-related grouping; average length of stay (ALOS); hospital staffing; CHIF revenue streams; and hospital incomes and expenditures., Results: During the study period, the cost-efficiency of Croatian public hospitals did not meaningfully improve. While ALOS decreased by 14% and the number of beds decreased by 12%, bed occupancy rates decreased by 9%, acute inpatient admissions by 5%, and diagnosis-related group (DRG)-weighted output by 16%. Hospitals operated at higher costs, as the average cost per DRG-weighted case increased by 17%, from HRK 11828 in 2016, to HRK 13897 in 2018., Conclusions: In this period, Croatian reforms failed to improve hospital efficiency. This may be explained by the failure of reformers to heed the experience of other countries, which showed that hospital payment reform of this nature calls for systematic and coordinated actions, inter-agency collaboration, and a strategic approach where the various interventions are in congruence and act to reinforce one another.

Stress urinary incontinence (SUI) is defined as a complaint of inadvertent loss of urine occurring as a result of an increase in intraabdominal pressure. Strong evidence supports the use of pelvic floor muscle training (PFMT) as the first-line conservative treatment for SUI. Extracorporeal magnetic stimulation (EMS) is a non-invasive, effective, acceptable, and safe therapeutic modality for SUI. Although PFMT and EMS share most of their influences on the pathophysiology of SUI, it is unclear whether one of these routinely used treatment modalities is superior to another in terms of improvement of clinical outcomes or cost-effectiveness. To the best of our knowledge, no randomized controlled trials have so far directly compared PFMT with EMS. Our aim here is to describe a protocol for such a study. This will be a parallel-group, single-blind, randomised controlled trial compliant with the SPIRIT, CONSORT, and TIDieR reporting guidelines. Participants will be women aged 18 to 65 years who have previously given at least one vaginal delivery (at least 12 months before joining the study) who present with symptoms of SUI lasting at least 6 months yet have not previously received treatment for it. In the first study arm, patients will receive an eight-week, high-intensity, home-based Kegel exercises regimen. In the second study arm, the treatment scheme will consist of 2 sessions of EMS per week for a total of eight weeks. The primary outcome will be effectiveness of treatment as measured by the International Consultation on Incontinence Questionnaire Urinary Incontinence-Short Form overall score, eight weeks, three months, and six months after commencement of treatment., Competing Interests: The authors report no conflict of interest., (Copyright © 2021 Termedia.)

Aim of the Study: Lateral episiotomy is a widely used procedure, although it is rarely mentioned in the literature and its effects on the pelvic floor are largely unexplored. The purpose of this study is to evaluate the impact of lateral episiotomy on the incidence of urinary incontinence (UI) after vaginal delivery in primiparas., Material and Methods: The study design is a prospective cohort study. The primiparas were divided into two groups. The first group consisted of women who gave birth with lateral episiotomy, while the second group included women who gave birth with an intact perineum or with perineal tears of first and second degree. Assessments of UI were performed at 5 and 8 months after childbirth using the International Consultation on Incontinence Questionnaire - Short Form (ICIQ-SF) questionnaire followed by the stress test., Results: The results revealed no significant differences ( p > 0.05) in emergence of stress urinary incontinence (SUI) between the groups at the two time points. There were no statistically significant differences in overall rate of UI, urge urinary incontinence (UUI), or mixed urinary incontinence according to the ICIQ-SF questionnaire. The overall incontinence rate on the first examination was 24% in the episiotomy group and 36% in the perineal laceration group, although the difference was not statistically significant ( p = 0.064). On the second examination, rates were similar and without a statistically significant difference., Conclusions: Lateral episiotomy has a neutral effect on the onset of UI in primiparous women in the first year after delivery., Competing Interests: The authors report no conflict of interest., (Copyright © 2021 Termedia.)

Objective: Although available diagnostic criteria are intelligible, combination of OAB and anxiety in the same patient presents a perfect example of medical causality dilemma, commonly stated as the question: "which came first: the chicken or the egg?". The aim of this review article is to address available insights in bidirectional association between OAB and anxiety., Methods: In this review article, we included different types of studies whose results are presented as relative risk (RR) or odds ratio (OR) with a 95% accuracy. A literature search was conducted with the use of the PubMed and EMBASE electronic databases focusing on identifying articles published in English between 1990 and 2020., Results: The electronic searches, after duplicate records removal, provided a total of 126 citations. Of these, 107 were excluded after title/abstract screening (not relevant to the review). We examined the full text of 19 publications remaining to summarize possible mechanisms between OAB and anxiety. According to examined literature, our result synthesis provides insight in epidemiology, pathophysiology, diagnostic and therapeutic approach of both conditions., Conclusion: Temporal relationship between OAB and anxiety is not very well documented because available longitudinal cohort studies are limited. The limitation of the published literature is that most were population-based symptom studies demonstrating high risk of bias. Although data from analysed studies suggest that anxiety and OAB and anxiety might be casually related, studies provided on clinical population are warranted. In addition to the traditional urologic factors, we recommend that psychosocial factors such as anxiety should be assessed routinely in patients with OAB.

Objectives: The present study was conducted with the aim to translate, adapt, and validate the 8-item Overactive Bladder Questionnaire (OAB-V8) in Croatia., Methods: This study included a total of 58 female patients with OAB and 66 healthy women. The translation to Croatian followed standardized procedure. All eligible participants completed OAB-V8 at inclusion and 2 weeks after to assess test-retest reliability. Cronbach α coefficient was calculated to assess internal consistency., Results: Our study demonstrated high internal consistency for all items at both visits (Cronbach α between 0.799 and 0.847), with stable internal consistency reliability across items during the 2-week period. However, the exception is the item "waking up at night to urinate," which significantly changed during the 2-week period. Intraclass correlation for OAB-V8 items ranged from 0.810 to 1.0, with Spearman correlations greater than 0.9 for all items (P < 0.01). There were strong significant correlations between frequency of urination during daytime and uncomfortable and sudden urge to urinate, and between nocturia and waking up at night. Discriminative validity showed statistically significant score differences between patients and the control group., Conclusions: The Croatian version of the OAB-V8 was successfully translated, adapted, and validated so the questionnaire is now ready for use as a reliable tool for initial screening and assessing patients with OAB in everyday Croatian clinical practice., Competing Interests: The authors have declared they have no conflicts of interest., (Copyright © 2021 American Urogynecologic Society. All rights reserved.)

Background: The COVID-19 pandemic disrupted hospital care, as hospitals had to deal with a highly infectious virus, while at the same time continuing to fulfill the ongoing health service needs of their communities. This study examines the direct effects of COVID-19 on the delivery of inpatient care in Croatia. Materials and Methods: The research is a retrospective, comparative analysis of the hospital admission rate across all Diagnosis Related Group (DRG) classes before and during the pandemic. It is based on DRG data from all non-specialized acute hospitals in Croatia, which account for 96% of national inpatient activity. The study also used COVID-19 data from the Croatian Institute of Public Health (CIPH). Results: The results show a 21% decrease in the total number of admissions [incident rate ratio (IRR) 0.8, p < 0.0001] across the hospital network during the pandemic in 2020, with the greatest drop occurring in April, when admissions plunged by 51%. The decrease in activity occurred in non-elective DRG classes such as cancers, stroke, major chest procedures, heart failure, and renal failure. Coinciding with this reduction however, there was a 37% increase (IRR 1.39, p < 0.0001) in case activity across six COVID-19 related DRG classes. Conclusions: The reduction in hospital inpatient activity during 2020, can be attributed to a number of factors such as lock-downs and quarantining, reorganization of hospital operations, the rationing of the medical workforce, and the reluctance of people to seek hospital care. Further research is needed to examine the consequences of disruption to hospital care in Croatia. Our recommendation is to invest multidisciplinary effort in reviewing response procedures to emergencies such as COVID-19 with the aim of minimizing their impact on other, and equally important community health care needs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kalanj, Marshall, Karol, Tiljak and Orešković.)

Introduction : To study the impact of biosimilars in assisted reproductive treatments, we performed a review of the literature. Biosimilars are a bioequivalent chemical drug referred to the original. Their production is strongly requested in order to reduce drug cost and reduce health economic impact on national health system. In assisted reproductive treatments different gonadotropin biosimilars are being produced. Areas covered : For this reason, we performed a review of the literature on follitropin alfa Gonal-F biosimilar, Ovaleap and Bemfola, to assess their cost efficacy in national health system. Cost effective (CE) analysis and incremental cost-effectiveness ratio (ICER) were used as parameters for biosimilar impact evaluation in the national health system economy. In particular, they had only slight impact on cost reduction of recombinant follitropin alfa products in Europe. Expert opinion : considering cost-effective analysis, Gonal-F remains the first choice for national health systems. However, well-designed powered methods are strongly needed to assess biosimilars cost-effectiveness.

Background: Patients with epilepsy commonly report sexual dysfunction (SD) and reproductive difficulties. This study aimed to evaluate the relationship between epilepsy, antiepileptic drugs (AEDs) and SD, and its association with the quality of life and depressive symptoms., Subjects and Methods: This was a prospective study carried out in a tertiary healthcare centre. SD was evaluated using the internationally acclaimed questionnaire Arizona Sexual Experiences Scale (ASEX) that was successfully translated into Croatian and validated for this purpose. Depressive symptoms and quality of life were evaluated using the Hamilton Rating Scale for Depression (HAM-D17) and Quality of life in epilepsy-31 inventory (QOLIE-31)., Results: Of 108 patients (68 (63 %) women, 40 (37 %) men, mean age 39.54±15.91 (range18-80) years) with epilepsy, 16 (14.8%) had focal, 38 (35.2%) generalized and 44 (40.7%) both types of epilepsy. Mean overall total score on the ASEX questionnaire was 11.94±5.61 (mean total score women 12.85±6.00, mean total score men 10.4±4.55), with 48 reporting that they had sexual activity in the past week. Nine (8.33%) patients (7 (6.48%) women, 2 (1.85%) men, mean age 47.66±19.33 (range 25-80) years) had a score 19 and above, 38 (35.18%) patients (27 (25%) women, 9 (8.33%) men, mean age 46.82±17.78 (range 19-80) years) individual score 5 and above on any one item, and 33 (30.55%) patients (26 (24.07%) women, 7 (6.48%) men, mean age 48.87±17.8 (range 19-80) years) had an individual score 4 and above on any three items. Significant correlations were found between SD and older age (p=0.001) and between more pronounced symptoms regarding SD on ASEX and female gender (p=0.000). There were no significant correlations between the type of epilepsy and SD, nor between the AEDs (old generation vs. modern) and SD. Significant correlations were found between the SD and more pronounced depressive symptoms (p=0.003) and between the SD and a lower quality of life (p=0.001)., Conclusions: Results of our study suggest SD is experienced by around one-third of patients in our group, which is similar to the previous percentage of SD reported in the community sample. Women were found to experience more pronounced symptoms of SD on ASEX. Symptoms of SD were found to be significantly correlated with older age, female gender, lower quality of life and depressive symptoms, while no significant correlations were found with the type of epilepsy and the AEDs.

Aim: To assess the attitude about the importance of introducing education on artificial intelligence (AI) in medical schools' curricula among physicians whose everyday job is significantly impacted by AI., Methods: An anonymous questionnaire was distributed at the national level in Croatia among radiologists and radiology residents practicing in primary, secondary, and tertiary health care institutions, both in the private and the public sectors. The overall response rate was 45% (144 of 321)., Results: A large majority of participants - 89.6% (95% Agresti-Coull confidence interval 0.83-0.94) agreed on the need for education on AI to be included in medical curricula. Answers revealed a very high support across age groups and regardless of subspecialty area. A slightly higher support was present among physicians working in university hospitals compared with those in primary care centers, and among radiology residents compared with radiologists - but these estimated differences are uncertain, and the support levels were clearly high across the considered variables., Conclusion: Since medical students have previously been shown to support introducing education on AI, a growing literature argues the same for reasons here reviewed, and physicians practicing a highly relevant area (radiology) overwhelmingly agree, we conclude that medical schools should indeed take steps to keep pace with technological progress in medicine by including education on AI in their curricula, be it as part of existing or new courses.

Bladder exstrophy (BE) is a rare congenital malformation estimated to occur in up to 1/250,000 female live births. The evidence supporting the incidence, uterine preservation and its overall fertility rate in patients with pelvic organ prolapse (POP) and BE is not precisely determined. We report a case of BE and POP in a 27-year-old nulliparous Caucasian. Due to the patient's strong fertility desire, considering her extensive surgical history background, our approach was to correct POP via the Manchester-Fothergill procedure. After 36 months, the patient was still asymptomatic with no evidence for prolapse recurrence. This case demonstrates diagnostic challenges and surgical dilemmas in treatment strategy for patients with BE and co-existent POP. Furthermore, routine long-term surveillance is necessary in terms of renal function, urinary continence, malignancy and possible obstetric issues.

Ovarian cancer (OC) is the most lethal female gynecological malignancy, mostly due to diagnosis in late stages when treatment options are limited. Hedgehog-GLI (HH-GLI) signaling is a major developmental pathway involved in organogenesis and stem cell maintenance, and is activated in OC. One of its targets is survivin ( BIRC5 ), an inhibitor of apoptosis protein (IAP) that plays a role in multiple processes, including proliferation and cell survival. We wanted to investigate the role of different GLI proteins in the regulation of survivin isoform expression (WT, 2α, 2B, 3B, and Δex3) in the SKOV-3 OC cell line. We demonstrated that survivin isoforms are downregulated in GLI1 and GLI2 knock-out cell lines, but not in the GLI3 knock-out. Treatment of GLI1 knock-out cells with GANT-61 shows an additional inhibitory effect on several isoforms. Additionally, we examined the expression of survivin isoforms in OC samples and the potential role of BIRC5 polymorphisms in isoform expression. Clinical samples showed the same pattern of survivin isoform expression as in the cell line, and several BIRC5 polymorphisms showed the correlation with isoform expression. Our results showed that survivin isoforms are regulated both by different GLI proteins and BIRC5 polymorphisms in OC.

BACKGROUND Ophthalmia neonatorum, or neonatal conjunctivitis, is an acute infection that occurs within the first 28 days of life. This aim of this survey was to evaluate the current methods of preventive treatment for ophthalmia neonatorum in maternity hospitals in Croatia. MATERIAL AND METHODS The annual hospital birth rate in Croatia is approximately 40,000. A clinical survey was undertaken with data collected using questionnaires sent to all 32 maternity hospitals in Croatia. There was a 100% response rate to the questionnaires. RESULTS Preventive treatment for ophthalmia neonatorum was administrated to all newborns in 75% (24/32) of Croatian maternity hospitals. In 45.8% of maternity hospitals, (11/32) these procedures were performed within the first hour after birth. In 54.2% of maternity hospitals (13/32), preventive treatment for ophthalmia neonatorum was administrated to all newborns from one to three hours after birth. The main treatment agent was tobramycin (83.3%). Other topical prophylactic treatments included povidone-iodine (8.3%), erythromycin (4.2%), and silver nitrate (4.2%). In 25% of obstetric units, prophylaxis for ophthalmia neonatorum was not used routinely, but in cases of diagnosed neonatal conjunctivitis, antibiotic treatment with tobramycin was mainly used. CONCLUSIONS A survey of all 32 maternity hospitals in Croatia showed variation in the prevalence of preventive treatment for ophthalmia neonatorum and the methods used. These findings support the need to implement standardized preventive measures that both conform to international clinical guidelines and recognize treatment availability in Croatia, where topical povidone-iodine is currently preferred for the prevention of ophthalmia neonatorum.

The aim of this review is to analyze the role of obesity on fertility outcome in women undergoing in vitro fertilization (IVF) with respect to clinical or live birth rates and pregnancy loss rates. Despite findings from several earlier and newer studies that obesity does not adversely affect pregnancy outcome in women attempting conception, numerous reports from mostly recent studies suggest that obesity undoubtedly impairs IVF outcomes. Obesity impairs ovarian responsiveness to gonadotrophin stimulation, requiring higher doses of medication, increased risk of cycle cancelation, pre-term delivery, low birth weight or miscarriage, and decreases implantation, clinical pregnancy or live birth rates compared to women of normal weight. The mechanisms underlying the adverse effects of female obesity on IVF outcome may be primarily explained by functional alterations to the hypothalamic-pituitary-ovarian axis. Additionally, obesity appears to affect deleteriously the number and quality of oocytes or embryos, and impairs endometrial decidualization which is necessary for uterine receptivity. Nevertheless, attaining normal body weight by the use of lifestyle modifications, including a healthy diet and exercise over time of several months before and during an IVF treatment, may be successful in achievement of gradual and sustainable weight loss with improvement of IVF outcome.

The aim of the review is to establish sexual and reproductive functions in men with spinal cord lesion (SCL). Many sexual and reproductive dysfunctions may be found in these patients including individual's low self-esteem, delay of orgasm, erectile or ejaculatory disorder and abnormalities of semen, which are characterized by lower sperm motility or viability. Owing to improvements in physical medicine and rehabilitation, the focus has been shifted from keeping patients alive towards ensuring the quality of life and improvements of sexual dysfunctions and later reproduction. Erectile dysfunction can be treated by using phosphodiesterase-5 inhibitors, intracavernosal injections, vacuum devices and penile prostheses. Semen can be retrieved from anejaculatory patients by medically assisted methods utilizing penile vibratory stimulation, electroejaculation, prostate mas-sage, or surgically. Although there is low chance for pregnancy in natural way in most of SCL pa-tients, fatherhood is possible through the introduction of assisted medical management. By use of various medical, technical and surgical procedures for sperm retrieval combined with assisted reproductive methods, high pregnancy rates have been reported comparable to those in able-bodied subfertile patients. Nevertheless, future studies are needed to improve semen quality and methods of assisted ejaculation in patients with SCL.

Hedgehog signaling pathway has been implicated in the pathology of ovarian cancer, and Survivin (BIRC5) has been suggested as a novel target of this pathway. Herein we investigated the role of Hedgehog signaling pathway and Survivin in ovarian carcinoma and borderline tumor samples. We aimed to determine possible ways of pathway modulation on primary ovarian cancer cells and an established cell line. RNA was extracted from fresh tumors and control tissues and gene expression was examined using qRT-PCR. Pathway activity in cell lines was examined after treatment with cyclopamine, SHH protein, GANT-61 or lithium chloride using qRT-PCR, western blot and confocal microscopy. The difference between control tissue, borderline tumors and carcinomas can be seen in GLI1 and SUFU gene expression, which is significantly higher in borderline tumors compared to carcinomas. SUFU also shows lower expression levels in higher FIGO stages relative to lower stages. BIRC5 is expressed in all tumors and in healthy ovarian tissues compared to our control tissue, healthy fallopian tube samples. Primary cells developed from ovarian carcinoma tissue respond to cyclopamine treatment with a short-term decrease in cell proliferation, downregulation of Hedgehog pathway genes, including BIRC5, and changes in protein dynamics. Stimulation with SHH protein results in increased cell migration, while GLI1 transfection or PTCH1 silencing demonstrate pathway upregulation. The pathway activity can be modulated by LiCl at the GSK3β-SUFU-GLI level, suggesting at least partial non-canonical activation. Downregulation of the pathway with GANT-61 has proved to be more effective than cyclopamine. GLI inhibitors may be a superior treatment option in ovarian cancer compared to SMO inhibitors.

The role of macroprolactinemia in women with hyperprolactinemia is currently controversial and can lead to clinical dilemmas, depending upon the origin of macroprolactin, the presence of hyperprolactinemic symptoms and monomeric prolactin (PRL) levels. Macroprolactinemia is mostly considered an extrapituitary phenomenon of mild and asymptomatic hyperprolactinemia associated with normal concentrations of monomeric PRL and a predominance of macroprolactin confined to the vascular system, which is biologically inactive. Patients can therefore be reassured that macroprolactinemia should be considered a benign clinical condition, resistant to antiprolactinemic drugs, and that no diagnostic investigations or prolonged follow-up should be necessary. However, a significant proportion of macroprolactinemic patients appears to suffer from hyperprolactinemia-related symptoms and radiological pituitary findings commonly associated with true hyperprolactinemia. The symptoms of hyperprolactinemia are correlated to the levels of monomeric PRL excess, which may be explained as coincidental, by dissociation of macroprolactin, or by physiological, pharmacological and pathological causes. The excess of monomeric PRL levels in such cases is of primarily importance and the diagnosis of macroprolactinemia is misleading or inadequate. However, macroprolactinemia of pituitary origin associated with radiological findings of pituitary adenomas may rarely occur with similar hyperprolactinemic manifestations, exclusively due to bioactivity of macroprolactin. Therefore, in such cases with hyperprolactinemic signs and pituitary findings, macroprolactinemia should be considered a pathological biochemical condition of hyperprolactinemia. Accordingly, individualized diagnostic investigations with the introduction of dopamine agonists, or other treatment with prolonged follow-up, should be mandatory. The review analyses the laboratory and clinical significance of macroprolactinemia in hyperprolactinemic women suggesting clinically useful diagnostic and treatment strategies., (Copyright © 2017. Published by Elsevier B.V.)

The aim of this review is to analyse the effectiveness of exogenous kisspeptin administration as a novel alternative of triggering oocyte maturation, instead of currently used triggers such as human chorionic gonadotropin (hCG) or gonadotropin releasing hormone (GnRH) agonist, in women undergoing in vitro fertilisation (IVF) treatment. Kisspeptin has been considered a master regulator of two modes of GnRH and hence gonadotropin secretion, pulses and surges. Administration of kisspeptin-10 and kisspeptin-54 induces the luteinising hormone (LH) surge required for egg maturation and ovulation in animal investigations and LH release during the preovulatory phase of the menstrual cycle and hypothalamic amenorrhoea in humans. Exogenous kisspeptin-54 has been successfully administered as a promising method of triggering oocyte maturation, following ovarian stimulation with gonadotropins and GnRH antagonists in women undergoing IVF, due to its efficacy considering achieved pregnancy rates compared to hCG and GnRH agonists. Also, its safety in patients at high risk of developing ovarian hyperstimulation syndrome is noteworthy. Nevertheless, further studies would be desirable to establish the optimal trigger of egg maturation and to improve the reproductive outcome for women undergoing IVF treatment.

The purpose of this review is to analyze current medical strategies in the prevention of ovarian hyperstimulation syndrome (OHSS) during ovarian stimulation for in vitro fertilization. Owing to contemporary preventive measures of OHSS, the incidence of moderate and severe forms of the syndrome varies between 0.18% and 1.40%. Although none of medical strategies is completely effective, there is high-quality evidence that replacing human chorionic gonadotropin (hCG) by gonadotropin-releasing hormone (GnRH) agonists after GnRH antagonists and moderate- quality evidence that GnRH antagonist protocols, dopamine agonists and mild protocols reduce the occurrence of OHSS. Among various GnRH agonists, buserelin 0.5 mg, triptorelin 0.2 mg and leuprolide acetate (0.5-4 mg) have been mostly utilized. Although GnRH trigger is currently regarded as the best tool for OHSS prevention, intensive luteal support with exogenous administration of estradiol and progesterone or low-dose hCG on the day of oocyte retrieval or on the day of GnRH agonist trigger are required to achieve optimal conception rates due to early luteolysis. Among currently available dopamine agonists, cabergoline, quinagolide and bromocriptine are the most common drugs that should be used for prevention of both early and late OHSS. Mild stimulation protocols offer attractive option in OHSS prevention with satisfactory pregnancy rates.