Early Maturation of Corpus Luteum in Rabbits - Effect of Sildenafil Citrate on Luteolytic Capacity in the Early Luteal Period

Background:  Prostaglandin F2 alpha (PGF2α) binds to the specific receptor (PTGFR) on the corpus luteum (CL) in mammals, inducing regression of the CL structure (luteolysis) and initiating a new cycle. While PGF2α is effective only on mature CL, the immature CL structure (early luteal phase) resists PGF2α. In this study, sildenafil citrate, which is used to increase blood flow in the genital organs for treating specific pregnancy issues in women, was administered during the early luteal phase in a rabbit model to test the hypothesis of enhancing blood flow to the CL, thereby promoting earlier maturation and enabling a response to PGF2α. Materials, Methods & Results: The study was conducted in 2 sub-studies: clinical and molecular. A large number of rabbits were initially included in the sub-studies to ensure a sufficient number of pseudo-pregnant rabbits. Ovulation in rabbits was induced with buserelin acetate and was considered as day 0 of the study. The sub-studies were continued with rabbits whose pseudo-pregnancies were confirmed according to progesterone (P4) results. As a result, the studies were continued with a total of 41 pseudo-pregnant New Zealand female rabbits, 21 of which were included in the clinical sub-study and 20 in the molecular sub-study. In both sub-studies, on day 3 of the luteal period, rabbits in the treatment group received 5 mg/kg sildenafil citrate and all rabbits received a single dose of exogenous PGF2α on day 4 to induce luteolysis. In the clinical sub-study, echotexture and intraovarian blood flow changes in the ovaries were determined by ultrasonography (USG) examination. In the molecular sub-study, the expression changes of Hypoxia Inducible Factor 1 Alpha (HIF1A) and Vascular Endothelial Growth Factor (VEGF) related to angiogenesis, Steroidogenic Acute Regulatory Protein (StAR) related to P4 metabolism, Prostaglandin-Endoperoxide Synthase 2 (PTGS2) related to prostaglandin (PG) mechanism and 15-Hydroxyprostaglandin Dehydrogenase (HPGD) genes at mRNA level were determined using Real Time Polymerase Chain Reaction (RT-PCR) in CL tissues obtained with ovariohysterectomy (OVH) at 1 and 12 h after PGF2α injection. In addition, blood samples were collected for determine P4 levels from all rabbits. In the clinical sub-study; there was no difference between the groups in mean gray values (MGV), whereas there was a significant decrease in both pulsatile index (PI) and resistance index (RI) values at 40 min after PGF2α injection (P < 0.05). In the molecular sub-study, it was determined that sildenafil citrate had no significant effect (P > 0.05) on the expression levels 1 and 12 h after PGF2α injection.  According to the results of the molecular sub-study, no significant effect of sildenafil citrate on the mRNA expression levels in the investigated genes was detected (P > 0.05). However, within each group, differences were found according to OVH time after PGF2α injection. It was observed that PTGS2 and HPGD mRNA expressions decreased at the 12th h compared to the 1st h, while HIF1A expression increased (P < 0.05). Discussion: According to the results obtained from clinical and molecular sub-studies, it was determined that a single dose of sildenafil citrate (5 mg/kg) applied on the 3rd day of the luteal period did not contribute to the maturation process of the CL, did not increase blood flow, and was insufficient to break the resistance of the CL against PGF2α applied on the 4th day of the luteal period. However, a significant decrease in the PI value at the 40th min after PGF2α injection suggests that sildenafil citrate has a supportive effect, and that this decrease is also seen in the RI value, suggesting that its effect is insufficient against the vasoconstrictive effect of PGF2α. Keywords: sildenafil citrate, PGF2 alpha, corpus luteum, early luteal stage, rabbit

The efficacy of multiparametric prostate magnetic resonance imaging in the diagnosis and treatment of prostate cancer

Aim: To investigate the accuracy of multiparametric prostate magnetic resonance imaging (mpMRI) in determining the diagnosis and treatment options of prostate cancer (PCa), and its pathology correlation. Methods: Between October 2017 and January 2018, 73 patients were subjected to an mpMRI at our clinic. Of these patients, 11 were radical prostatectomy (RP) after treatment, and four were post- radiation therapy (RT) follow-up. The remaining 58 patients were assigned to the PSA elevation and / or positive digital rectal examination (DRE) patient group in this study and their outcomes were evaluated. Results: Of the 58 patients included in the study, 13 were found to have a PI-RADS 5 on mpMRI and in 9 (90%) of 10 patients undergoing simultaneous biopsy, PCa was detected. The biopsy results of all cases evaluated as PI-RADS 1 were benign. All of the patients who were ISUP 3 and above had a PI-RADS 5. Patients with a PI-RADS score of 4 and above being ISUP 2 and above was statistically significant (p=0.011). A case had undergone a previous radical prostatectomy assessment revealed that tPSA increased to 2 ng/ml during the follow-up, and so RT was added to the treatment; although LAP was identified in the left iliac region on an mpMRI performed upon the continued increase of tPSA. During the follow-ups of the patient who had regional RT, the tPSA dropped below 0.01 ng/ml. Conclusion: The results of our study show that mpMRI can gain a new and important place in urology due to the guidance it provides in biopsies, facilitating targeted biopsy, its effectiveness in determining treatment modalities and its importance in post-PCa treatment follow-ups

Can proliferative hypertrophic scars of the median sternotomy incision predict the occurrence and characteristics of urethral stricture?

Conclusion: A poorly healed median stemotomy incision scar can predict a poor wound healing in the urethra tissue. Further large scale, multi-center and prospective studies are needed to clarify this relationship

Prognostic value of systemic inflammation response index in patients with persistent human papilloma virus infection

Objectives: Persistent human papilloma virus (HPV) infection is a risk factor for the progression of cervical neoplasia into invasive carcinoma. Many inflammatory markers obtaining from hemogram parameters as platelets, monocytes, lymphocytes, and neutrophils or their ratios are still under investigation in recent decades, especially in the oncology era. Indeed, there have not been enough data about the relationship between these parameters and cervical cancer in the literature. Our primary aim was to investigate the possible relationship between the persistent HPV, which is one of the significant risk factors of cervical cancer, and these inflammatory markers. Further, we can add an easy follow-up parameter in women with persistent HPV infection. Material and methods: The study included patients between 30–65 years old, tested positive for HPV, and afterward had an HPV control test between January 2015 and June 2020. Results: The study included 114 HPV DNA-positive patients. The mean age was 43 (standard deviation 8.7), and 41 of them (36%) had persistent HPV, but the remaining 73 (64%) did not. The baseline neutrophil/lymphocyte ratio (NLR) value was 2.1, platelet/lymphocyte ratio (PLR) was 133, monocyte/lymphocyte ratio (MLR) was 0.28, and systemic inflammation response index (SIRI) was 0.9. All the parameters were significantly higher in the persistent HPV group compared to the non-persistent group. Patients who had 0.65 and under this had a significantly lower risk of persistent HPV. Conclusions: Persistent HPV disease can be predicted with an elevated SIRI, NLR, and other hematologic parameters. So, we can closely follow up with these patients with different algorithms to prevent cervical cancer

Plasma profile of Pregnancy Associated Glycoproteins during Postpartum period in Konya Merino ewes lambing single and twin

This study investigated the plasma profile of Pregnancy Associated Glycoproteins (PAGs) after lambing in Konya Merino ewes using specific cattle pregnancy test kit. A total of 16 Konya Merino ewes were used as a material. Four groups were set up, ewes birthing a male lamb (SM group, n=4), a female lamb (SF group, n=4), twin male lambs (TM group, n=4) or twin female lambs (TF group, n=4). Blood plasma samples were taken on days 0 (lambing day), 3, 7, 10, 14 and then weekly until day 35. All samples were analysed using a bovine pregnancy test kit to detect of PAGs level. It was determined that there was a strong negative correlation between PAGs levels in peripheral blood and days after lambing (r2=0.969; P<0.01). However, no relationship was found between PAGs level and lamb gender or birth type. In conclusion, plasma PAGs level decreases rapidly in Konya Merino ewes regardless of lamb gender and birth type. Moreover, the results showed that the plasma profile of PAGs after lambing in Konya Merino ewes can be monitored with a bovine commercial ELISA–based pregnancy test kit, and the test results can be used in decisions and assessments based on the levels of PAG molecules

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Assessing the queuing process using data envelopment analysis:an application in health centres

Queuing is one of the very important criteria for assessing the performance and efficiency of any service industry, including healthcare. Data Envelopment Analysis (DEA) is one of the most widely-used techniques for performance measurement in healthcare. However, no queue management application has been reported in the health-related DEA literature. Most of the studies regarding patient flow systems had the objective of improving an already existing Appointment System. The current study presents a novel application of DEA for assessing the queuing process at an Outpatients’ department of a large public hospital in a developing country where appointment systems do not exist. The main aim of the current study is to demonstrate the usefulness of DEA modelling in the evaluation of a queue system. The patient flow pathway considered for this study consists of two stages; consultation with a doctor and pharmacy. The DEA results indicated that waiting times and other related queuing variables included need considerable minimisation at both stages

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication