Type III-B CRISPR-Cas cascade of proteolytic cleavages.

The generation of cyclic oligoadenylates and subsequent allosteric activation of proteins that carry sensory domains is a distinctive feature of type III CRISPR-Cas systems. In this work, we characterize a set of associated genes of a type III-B system from Haliangium ochraceum that contains two caspase-like proteases, SAVED-CHAT and PCaspase (prokaryotic caspase), co-opted from a cyclic oligonucleotide-based antiphage signaling system (CBASS). Cyclic tri-adenosine monophosphate (AMP)-induced oligomerization of SAVED-CHAT activates proteolytic activity of the CHAT domains, which specifically cleave and activate PCaspase. Subsequently, activated PCaspase cleaves a multitude of proteins, which results in a strong interference phenotype in vivo in Escherichia coli. Taken together, our findings reveal how a CRISPR-Cas-based detection of a target RNA triggers a cascade of caspase-associated proteolytic activities.

The effect of platelet-rich plasma on intra-abdominal adhesions in rabbit uterine horn model.

OBJECTIVE: This study was carried out to investigate the effect of autologous platelet-rich plasma (PRP) on intra-abdominal adhesion at the cesarean section incision line in the uterus. MATERIAL AND METHODS: As experimental animals 16 white New Zealand rabbits, 5-months-old, unmated, were used. Animals were divided into two groups the control group and PRP application group. In each group, a transverse incision was made to the uterus to mimic the cesarean section and sutured. Relaparotomy was performed 21 days after the first operation. RESULTS: When the groups were evaluated in terms of inflammation, there was a significant difference between the two groups. When the groups were evaluated in terms of Mason's Trichrome staining and fibrosis, There was a significant difference between groups. When the groups were evaluated in terms of vascular endothelial growth factor-1, there was also a significant difference between the groups. In an experimental rabbit uterine horn adhesion model, PRP is effective in preventing post-operative adhesion formation. CONCLUSIONS: This result may guide clinical studies using autologous PRP to prevent post-operative adhesion formation after gynecological operations.

OBJETIVO: Este estudio se llevó a cabo para investigar el efecto del plasma rico en plaquetas (PRP) autólogo sobre la adhesión intraabdominal en la línea de incisión de la cesárea en el útero. MATERIAL Y MÉTODOS: Como animales de experimentación se utilizaron 16 conejos blancos de Nueva Zelanda, de 5 meses de edad, sin aparear. Los animales se dividieron en dos grupos como grupo de control y grupo de aplicación de PRP. En cada grupo, se hizo una incisión transversal al útero para imitar la cesárea y se suturó. La relaparotomía se realizó 21 días después de la primera operación. RESULTADOS: Cuando los grupos se evaluaron en términos de inflamación, hubo una diferencia significativa entre los dos grupos. Cuando los grupos se evaluaron en términos de tinción MT y fibrosis, hubo una diferencia significativa entre los grupos. Cuando los grupos se evaluaron en términos de VEGF-1, también hubo una diferencia significativa entre los grupos. En un modelo experimental de adherencia al cuerno uterino de conejo, el PRP es eficaz para prevenir la formación de adherencias posoperatorias. CONCLUSIONES: Este resultado puede guiar los estudios clínicos que utilizan PRP autólogo para prevenir la formación de adherencias postoperatorias después de operaciones ginecológicas.

Women's aesthetic perceptions of the genitalia and their association with anatomical measurements.

BACKGROUND: The purpose of this study is to determine women's perceptions of the vulva with the criteria defined in the literature for the ideal vulva and determine their relationship with anatomical measurements to determine the extent to which women's perceptions of normal align with our aesthetic standards of normality. METHODS: First of all, a questionnaire was given to all participants. The items of the data collection form included personal information, obstetric and gynecological information, their perceptions of their external genitalia and any physical, sexual, psychological, and hygiene problems they experience. Then examination and measurements of the external genitalia were performed. RESULTS: The majority of participants considered their genitalia normal (n = 101, 89.4%), while 12 participants (10.6%) considered them abnormal. Statistical analyses showed that women's perception of their genitalia as normal in appearance and size was associated with labia minora asymmetry (p = 0.023 and p = 0.006, respectively) and hyperpigmentation (p = 0.010 and p = 0.047, respectively) but not with labia minora measurements or protrusion (p > 0.05). CONCLUSIONS: Although there is a tendency in the field of aesthetic surgery to define ideals and aesthetic standards for all parts of the body, our definitions of normality do not always coincide with those of the individual. The appearance of the genitalia is as personal as the face, and an individual's self-perception is more important than our ideal. LEVEL IV: Evidence obtained from multiple time series with or without the intervention, such as case studies. Dramatic results in uncontrolled trials might also be regarded as this type of evidence.

The role of cytokeratin 19 levels in the determination of endometriosis stages.

OBJECTIVE/AIM: Endometrisosis, one of the most common gynecological disease, is characterized by the presence of endometriotic tissue outside of uterine cavity. The development and the validation of a simple blood biomarker specific and sensitive for endometriosis may facilitate the rapid and the accurate diagnosis of the disease and thus early treatment. Cytokeratin expression changes during epithelial differentiation and this expression is important for the modulation and the control of cell cycle regulation, tumor cell motility and apoptosis. Cytokeratin 19 (CK-19) is expressed in most simple epithelial cells and their malignant counterparts. The aim of this study is to investigate serum CK-19 expression levels in patients with endometriosis and to determine the diagnostic role of CK-19 levels in differentiating various stage of endometriosis. METHODS: Ctytokeratin-19 expression and level were studied in 70 endometriosis patients and 50 volunteers by ELISA and RT-PCR. ROC analysis was performed by comparing all stages with each other and with the control group. RESULTS: The CK-19 levels were significantly higher in the endometriosis groups than that of the control group by ELISA and RT-PCR. A significant (p < .05) difference was observed in endometriosis patients according to the stages. CONCLUSION: Based on our data, it suggests that Cytokeratin-19 may have a potential role in the development of endometriosis.

Circulating serum miR-200c and miR-34a-5p as diagnostic biomarkers for endometriosis.

OBJECTIVE: Endometriosis is defined by the presence of endometrial glands and stroma grow in areas outside the uterus. A simple blood test for endometriosis-specific biomarkers would offer a more timely accurate diagnosis of the disease and could lead to earlier treatment intervention. Alterations in microRNA (miRNA) levels in blood may reflect changes during normal physiologic processes and have been related to several pathologic conditions, including gynecologic diseases. In the present study, we aim to evaluate the level of serum miR-34a-5p and miR-200c from women with and without endometriosis, and to explore the potential of miRNAs as reliable non-invasive biomarkers in the diagnosis of endometriosis. METHODS: Expression levels of miRNAs were performed by quantitative real-time polymerase chain reaction (qRT-PCR). Serum cancer antigen 125 (CA-125) levels were analyzed by autoanalyzer. RESULTS: miR-34a-5p expression levels were decreased and miR-200c expression levels were increased in the endometriosis patients compared to the control group. According to the areas under the ROC curve (AUC) values, miR-200c and miR-34a-5p may serve as biomarkers for the diagnosis of endometriosis. Serum miR-34a-5p and miR-200c had a sensitivity of 78.95 % and 100 % and a specificity of 49.12 % and 100 %, respectively, for the detection of endometriosis. CONCLUSION: Serum miRNAs may provide a promising opportunity for diagnosis of endometriosis. Understanding the role of circulating miRNAs will serve a better comprehension of the systemic effects of endometriosis and offer options for new treatments. It is clear that more work is needed in this area.

Determination of PD-1 expression in peripheral blood cells in patients with endometriosis.

In patients with endometriosis, ectopic endometrial tissues can escape from immune system control and survive in other tissues. The pathophysiology of endometriosis is still not fully understood. In this study, we aimed to clarify the pathophysiology of endometriosis, which is thought to be a benign but infiltrative cancer type, which has many similarities with cancer biology by determining PD-1 expression in patients with endometriosis. In this study, n = 73 cases who underwent surgery or examination at the Obstetrics and Gynecology Clinic of Sivas Cumhuriyet University Faculty of Medicine and diagnosed as endometriosis in the biopsy material taken with the pre-diagnosis of endometriosis constituted the patient group. The control group consisted of n = 64 healthy subjects without concomitant malignancy or chronic inflammatory disease. Venous whole blood samples were obtained from the study groups. PD-1 and PD-L1 levels were determined by the ELISA method from serum and plasma samples. PD-1 gene expression level was determined by RT-PCR. The PD-1 level was found to be approximately 350 ± 150 ng/L and 45 ± 17 ng/L in endometriosis and control group, respectively. While the PD-L1 level was approximately 760 ± 108 ng/L in the patients, this level was 140 ± 14 ng/L in the controls. According to the RT-PCR results, the expression of the PD-1 gene 10 times higher compared to the controls. Conclusion: The identified increase of PD-1 levels and gene expression in endometriosis groups show that immunotherapy may be used in the treatment of endometriosis.

Genetic variants in the microRNA machinery gene (Dicer) have a prognostic value in the management of endometrial cancer.

AIM: Although several associations were found between Dicer rs3742330 single nucleotide polymorphism (SNP) and development and prognosis of some epithelial cancers, relationship between the SNP rs3742330 and endometrial cancer (EC) has not yet been studied. We aimed to investigate the prognostic role of rs3742330 SNP of Dicer gene in EC patients. SUBJECTS AND METHODS: A total of 80 EC patients and 80 control subjects included in the study. Real-time polymerase chain reaction and the allele discrimination technique was used for genotyping of rs3742330 SNP. RESULTS: There was no significant difference between EC patients and control subjects with regard to the genotype and allele frequencies for Dicer rs3742330 SNP (P > 0.05). Despite Dicer rs3742330 SNP had no prognostic value in terms of stage, grade, lymphovascular invasion, myometrial invasion, tumor size, and histopathology; malignant peritoneal cytology has been detected higher in the patients bearing AA genotype compare with AG genotype (P = 0.023). Higher recurrence rate and shorter time to recurrence were found in patients bearing AG and GG genotype compare with AA genotype (P = 0.009). CONCLUSION: Dicer rs3742330 AG and GG genotypes may have the potential to be used as a predictor of poor prognosis in the management of EC case.

Ovarian reserve is preserved in Behçet's disease.

AIM: To compare ovarian reserve with anti-müllerian hormone (AMH) levels, antral follicle counts (AFCs) and ovarian volume in patients with Behçet's disease (BD) and healthy subjects. METHOD: This study included 35 women with BD (mean age: 34.4 ± 5.3 years) and 35 healthy controls (mean age: 34.1 ± 6.0 years). Venous blood samples collected from groups on menstrual cycle Days 2-4 were analyzed using the enzyme-linked immunosorbent assay to measure follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2 ), prolactin (PRL) and AMH levels. The AFCs and ovarian volumes were estimated by ultrasonography on the same day. The body mass index (BMI), duration and severity of the disease, medications, and number of children were recorded. RESULTS: There was no statistically significant difference in the mean age, median gravida/para/abortus and the number of live births and mean BMI between the patient and control groups (P > 0.05). No statistically significant difference in the median FSH, LH, E2, PRL levels, right and left ovarian volumes, and right and left ovarian AFCs was observed among the patients and the controls (P > 0.05). There was no statistically significant difference in the mean AMH levels (P = 0.468). Bonferroni correction showed no statistically significant correlation between AMH levels and age, BMI, FSH, LH, E2, PRL levels, right and left ovarian AFCs, right and left ovarian volume (P > 0.025) among the controls and the patients. CONCLUSION: Our study results suggest that ovarian reserve is preserved in patients with BD. In addition, AMH levels of the BD patients were similar to levels of healthy subjects.

Examination of the Relationship between Umbilical Cord Blood Gas Values and Hearing Function in Neonates.

OBJECTIVE: The aim of the present study was to examine the relationship between the results of the transient otoacoustic emission (TEOAE) test used in neonatal hearing screening and the results of the umbilical cord blood (UCB) analysis in neonates. METHODS: This retrospective study included 209 neonates born in the obstetric unit at the 37th gestational week. Based on the results of the TEOAE test, the neonates included in the study were divided into two groups as the study group composed of those "REFER" (n=141) and the control group consisting those "PASS" (n=68) the test. The UCB sampling procedure was performed on all neonates. In the blood samples, the pH parameters were evaluated by using glass electrodes, and the pCO2 and pO2 parameters were evaluated directly by using sensitive electrodes. RESULTS: When the additional maternal diseases were compared with the TEOAE results, the ratio of hypothyroidism was found to be statistically higher in the study group (p<0.05). In terms of the pO2, pCO2, HCO3, and pH values obtained as a result of analyzing the UCB samples, there was no statistically significant difference between the groups (p>0.05). CONCLUSION: The results of the present study showed that there was no statistically significant difference between the results of UCB analysis and the TEOAE test. However, we believe that conducting a larger study evaluating other parameters and employing UCB analysis would be useful, and UCB evaluation, which is an inexpensive, easy and effective method in determining hypoxia in neonates, might be a significant marker in cases at risk of hearing loss.

Primary Sjögren's Syndrome Adversely Affects the Female Sexual Function Assessed by the Female Sexual Function Index: A Case-Control Study.

OBJECTIVES: This study aims to evaluate the sexual function of females with primary Sjögren's syndrome (pSS) in comparison to healthy females by using the Female Sexual Function Index (FSFI). PATIENTS AND METHODS: This case-control study included 31 female patients (mean age 46.0±10.2 years; range 30 to 68 years) with pSS and 27 healthy females (mean age 44.2±8.5 years; range 30 to 55 years) as control group. The sexual function of the participants was assessed by 19-item FSFI. RESULTS: Mean duration of pSS in the patient group was 35.9 months (range 3 to 264 months). Significantly higher number of pSS patients reported positive history for vaginal infection compared to controls (n=26, 83.9% vs. n=7, 25.9%, respectively; p<0.001) without any difference in endocervical culture result. Cervical smear assessment revealed more inflammation and atrophy in patient group compared to control group (p=0.001). Mean FSFI total score was significantly lower in patient group than control group (18.9±9.9 vs. 25.1±5.1, respectively; p=0.004). Similarly, five out of six domains of FSFI -arousal, lubrication, orgasm, satisfaction, and pain- were significantly lower in patient group. FSFI total and subscale scores, except for pain, were found to be negatively correlated with duration of pSS. CONCLUSION: The pSS causes sexual dysfunction in female patients. Furthermore, as disease duration increases, female sexual function decreases. Clinical management of female patients with pSS should cover the assessment of their sexual functionality and taking the necessary precautions to maintain satisfactory quality of life and treatment outcome.

Elevated Serum CD95/FAS and HIF-1α Levels, but Not Tie-2 Levels, May Be Biomarkers in Patients With Severe Endometriosis: A Preliminary Report.

STUDY OBJECTIVE: To evaluate serum values of cluster of differentiation 95 (CD95/FAS), hypoxia-inducible factor 1-alpha (HIF-1α), and tyrosine kinase receptor 2 (Tie-2) as possible biomarkers of disease presence and severity in women with endometriosis, and to characterize the changes in these values in women with stage I/II and stage III/IV endometriosis. DESIGN: Prospective study (Canadian Task Force classification I). SETTING: University hospital. PATIENTS: Thirty women with endometriosis and 30 healthy women without endometriosis. INTERVENTION: For the diagnosis of endometriosis and prediction of its severity, we measured the serum levels of CD95/FAS, which assess apoptotic conditions, and of HIF-1α and Tie-2, which assess angiogenesis. Endometriosis was diagnosed and staged through surgical laparoscopy and later confirmed histologically. During the surgery, the patients with endometriosis were divided into 2 groups based on disease stage. Eleven patients had stage I/II endometriosis, and 19 had stage III/IV endometriosis. MEASUREMENTS AND MAIN RESULTS: Endometriosis was associated with increased serum CD95/FAS and HIF-1α levels, but not Tie-2 levels. We also determined that stage III/IV endometriosis was associated with higher serum CD95/FAS and HIF-1α levels, but not Tie-2 levels, compared with stage I/II endometriosis. CONCLUSION: Endometriosis, in accordance with its severity, increases serum CD95/FAS and HIF-1α levels, but not Tie-2 levels. These biomarkers may be useful for reproductive surgeons to improve the quality of counseling women about the presence and severity of endometriosis.

Effect of imatinib on growth of experimental endometriosis in rats.

OBJECTIVE: Currently, medical and surgical treatment options for endometriosis are limited due to suboptimal efficacy, and also safety and tolerance issues. Long-term use of gonadotrophin-releasing hormone analogs, androgenes, and the danazol, which are widely used drugs for endometriosis, is usually not possible due to their suboptimal safety and tolerance profile. The lack of an effective, tolerable and safe treatment option for endometriosis makes animal models of experimental endometriosis necessary to study candidate drugs. The aim of this study was to investigate the efficacy of imatinib on the experimental endometriosis in a rat model. STUDY DESIGN: Endometriosis was induced by autotransplantation of uterine tissue into the peritoneal cavity. Twenty-four rats, which had visually confirmed endometriotic implants on subsequent laparotomy, were randomized into three groups to receive imatinib (25mg/kg/day, p.o.), anastrozole (0.004 mg/day, p.o.), or normal saline (0.1 mL, i.p.) for 14 days. After removal of endometriotic tissue and H & E staining, endometriosis score was determined according to a semiquantitative histological classification. Also, immunostaining with primary antibodies including VEGF, CD117, and Bax were used for immunohistochemical (IHC) examination. RESULTS: Both anastrozole and imatinib suppressed the growth of endometriotic tissue and reduced the number of ovarian follicles. Although the difference was not statistically significant, imatinib was less effective than anastrozole for treatment of endometriosis. CONCLUSION: Imatinib effectively treats experimental endometriosis by its inhibitor effects on angiogenesis and cell proliferation.

Comparison of Effectiveness of Laminaria versus Vaginal Misoprostol for Cervical Preparation Before Operative Hysteroscopy in Women of Reproductive Age: A Prospective Randomized Trial.

STUDY OBJECTIVE: To compare the effectiveness and safety of intracervical laminaria dilator versus intravaginal misoprostol administered before surgery to facilitate cervical dilation before operative hysteroscopy. DESIGN: A prospective randomized study (Canadian Task Force classification 1). SETTING: A university hospital. PATIENTS: A total of 150 women were assigned at random to the following groups: laminaria dilation (n = 50), misoprostol dilation (n = 50), and mechanical dilation (n = 50). INTERVENTIONS: Hysteroscopic surgery of intrauterine lesions. MEASUREMENTS AND MAIN RESULTS: In this study, 150 women were assigned at random to receive cervical priming with an intracervical laminaria dilator, 200 µg of intravaginal misoprostol, or a mechanical dilator before operative hysteroscopy. Cervical response, surgical outcome, and complications of operative hysteroscopy were assessed. Visual analog scale (VAS) pain scores were recorded in the misoprostol and laminaria dilation groups. Demographic variables of the study groups were comparable (p = .278-.988). The duration of cervical pretreatment was similar with the intracervical laminaria dilator and intravaginal misoprostol (p = .803); however, intravaginal misoprostol was associated with more adverse effects (p = .031). Compared with the misoprostol dilation group, in which all patients required additional cervical dilation, notably fewer patients in the laminaria dilation group required additional cervical dilation after cervical preparation (p = .001). VAS pain scores were significantly higher in the laminaria dilation group, however (p = .001). CONCLUSION: Cervical priming with an intracervical laminaria dilator before operative hysteroscopy reduces the need for cervical dilation and better facilitates hysteroscopic surgery compared with intravaginal misoprostol. Oral analgesic use may be required before the use of this device.

Well-differentiated abdominal liposarcoma: experience of a tertiary care center.

BACKGROUND: We presented abdominal liposarcoma cases diagnosed and managed in a tertiary care center and also conducted a literature review on main features of this tumor. METHODS: Chart reviews of eight cases were conducted, and clinical, surgical, histopathological, and follow-up data were recorded. RESULTS: Overall, complete surgical resection was performed with adjacent organ resection in 25% of cases, and radiotherapy was not administered. Recurrence was developed in only one case and died after 2 years and 3 months, and other cases are under follow-up without recurrence. Histopatological examinations revealed findings of well-differentiated liposarcoma. CONCLUSIONS: According to our surgical experience, the surgical margin positivity may not be a determining factor for the survival of patients with well-differentiated liposarcoma, and in the absence of macroscopic invasion, adjacent organ resection may not be required. Radiotherapy may not be preferred when complete resection of abdominal mass was achieved.

Effects of Pazopanib, Sunitinib, and Sorafenib, Anti-VEGF Agents, on the Growth of Experimental Endometriosis in Rats.

We aimed to compare the effects of pazopanib, sunitinib, and sorafenib on endometriotic tissue morphology and histological characteristics as well as ovarian reserve in a rat model. Experimental endometriosis was established in 32 rats. They were randomly divided into 4 groups (8 rats for each group) to administer study drugs: pazopanib, sunitinib, sorafenib, and normal saline. Histological examination with hematoxylin and eosin staining to determine endometriosis score and immunostaining with primary vascular endothelial growth factor (VEGF), CD117, and Bax antibodies were performed. Bilateral ovaries excised to determine the ovarian follicle number. The endometriosis score was significantly reduced by pazopanib compared to other study drugs and by sunitinib compared to sorafenib and normal saline (P < .05). Sorafenib did not affect endometriosis score (P > .05). The VEGF score was significantly decreased similarly by pazopanib, sunitinib, and sorafenib compared to normal saline (P < .05). The CD117 score was reduced by pazopanib and sunitinib similarly compared to both sorafenib and normal saline that provided similar effect on the score (P < .05). The Bax scores of all the groups were found similar (P > .05). No study drugs caused meaningful change in the ovarian follicle number (P > .05). Pazopanib reduces the growth of endometriotic implants. This effect may be related to the suppressive effect of pazopanib on the endometriotic tissue expressions of VEGF and CD117 but not Bax. The study drugs do not affect ovarian reserve. The inconsistent effects of study drugs regarding study parameters require further studies to elucidate the molecular bases of their effects on the growth of endometriotic implants.

Huge cystic lymphangioma mimicking ovarian malignancy: a case report.

Lymphangiomas are rare benign congenital malformations of the lymphatic system. Clinical presentation varies from asymptomatic masses to acute abdominal pain. A 25-year-old female who presented with acute onset of abdominal distension and severe pelvic pain is presented. As a palpable mass was found on the pelvic examination and ultrasonography demonstrated a hypoechoic cystic mass, an ovarian malignancy was suspected. Exploratory laparotomy was performed and revealed cystic lymphangioma of the sigmoid colon. The clinical, radiological and pathological findings of the patient are discussed with a brief review of the literature.

Spontaneous twin cervico-isthmic pregnancy in a grand multiparous woman.

Cervico-isthmic pregnancy is a rare form of ectopic pregnancy and is defined as the implantation of a fertilized ovum in the cervico-isthmic portion. The cause is unknown; local pathology related to previous cervical or uterine surgery may play a role, given an apparent association with a prior history of curettage or cesarean delivery. Transvaginal ultrasonography and ß-human chorionic gonadotrophin assays are useful for diagnosis. Here we report a case of spontaneous twin cervico-isthmic pregnancy in a grand multiparous patient who was diagnosed early in the first trimester with transvaginal ultrasonography. The pregnancy was terminated successfully with methotrexate. Methotrexate seems to be most successful at early gestational ages.