Histochemical and ultrastructural evaluation of myopic corneal lenticules based on refractive error.

BACKGROUND: This study aimed to investigate cell degeneration, apoptosis, and ultrastructural differences in refractive lenticules (RL) obtained using small incision lenticule extraction (SMILE) compared with spherical equivalence (SE) refraction values. METHODS: This study included 84 eyes from 42 patients. Patients were divided into two groups according to the SE values: those with values below 4 diopters (D) (Group 1) and above 4 diopters (D) (Group 2). Patients who did not belong to the same SE group were excluded from the study. One RL obtained from each patient was separated for light microscopy and immunohistochemical examinations, and another for transmission electron microscopy (TEM) examinations. Caspase-3 for apoptosis and alpha-smooth muscle actin (α-SMA) for cell degeneration were evaluated using immunohistochemical examinations. RESULTS: Histological analyses showed that the density of collagen fibres was greater in Group 1 than in Group 2. Glycoaminoglycan and glycoprotein staining intensities were also higher in Group 1. TEM observations showed that Group 1 had intact cell and nuclear membranes, peripheral heterochromatin, and large nuclei, while Group 2 showed heterochromatin condensation and fragmentation, increased intracellular vacuoles, and loss of cytoplasm. Immunohistochemical analyses revealed that α-SMA and caspase-3 were significantly higher in Group 2 than in Group 1 (p < 0.001 and p < 0.001, respectively). CONCLUSIONS: Cell degeneration and apoptosis were significantly more common in the RLs with high SE values after SMILE surgery. The tissue response induced by surgery was more severe in the RLs with high SE values. This should be considered when reusing RLs.

Identifying Clinical Characteristics of Hypoparathyroidism in Turkey: HIPOPARATURK-NET Study.

Hypoparathyroidism is an orphan disease with ill-defined epidemiology that is subject to geographic variability. We conducted this study to assess the demographics, etiologic distribution, treatment patterns and complication frequency of patients with chronic hypoparathyroidism in Turkey. This is a retrospective, cross-sectional database study, with collaboration of 30 endocrinology centers located in 20 cities across seven geographical regions of Turkey. A total of 830 adults (mean age 49.6 ± 13.5 years; female 81.2%) with hypoparathyroidism (mean duration 9.7 ± 9.0 years) were included in the final analysis. Hypoparathyroidism was predominantly surgery-induced (n = 686, 82.6%). The insulting surgeries was carried out mostly due to benign causes in postsurgical group (SG) (n = 504, 73.5%) while patients in nonsurgical group (NSG) was most frequently classified as idiopathic (n = 103, 71.5%). The treatment was highly dependent on calcium salts (n = 771, 92.9%), calcitriol (n = 786, 94.7%) and to a lower extent cholecalciferol use (n = 635, 76.5%) while the rate of parathyroid hormone (n = 2, 0.2%) use was low. Serum calcium levels were most frequently kept in the normal range (sCa 8.5-10.5 mg/dL, n = 383, 46.1%) which might be higher than desired for this patient group. NSG had a lower mean plasma PTH concentration (6.42 ± 5.53 vs. 9.09 ± 7.08 ng/l, p < 0.0001), higher daily intake of elementary calcium (2038 ± 1214 vs. 1846 ± 1355 mg/day, p = 0.0193) and calcitriol (0.78 ± 0.39 vs. 0.69 ± 0.38 mcg/day, p = 0.0057), a higher rate of chronic renal disease (9.7% vs. 3.6%, p = 0.0017), epilepsy (6.3% vs. 1.6%, p = 0.0009), intracranial calcifications (11.8% vs. 7.3%, p < 0.0001) and cataracts (22.2% vs. 13.7%, p = 0.0096) compared to SG. In conclusion, postsurgical hypoparathyroidism is the dominant etiology of hypoparathyroidism in Turkey while the nonsurgical patients have a higher disease burden with greater need for medications and increased risk of complications than the postsurgical patients.

Transcervical Foley balloon catheter and vaginal prostaglandin E2 insert combination vs. vaginal prostaglandin E2 insert only for induction of labor at term: a randomized clinical trial.

PURPOSE: To analyze the effect of combined application of intravaginal PGE2 insert and intracervical Foley balloon catheter for induction of labor. METHODS: Patients with unfavorable cervices who required induction of labor from August 2017 to December 2017 were evaluated for the study. Three hundred and ten participants were randomly assigned to study (n:155) and control group (n:155). Nine patients in study group and seven patients in control group were excluded, because they declined to participate in the study. Totally, 294 women analyzed in this prospective randomized study: Group 1 (control group): labor induction with intravaginal PgE2 vaginal insert alone (n = 148) and Group 2 (study group): intracervical Foley balloon catheter insertion adjunct to the intravaginal PgE2 insert (n = 146). The primary outcome of our study was the period from induction to delivery. The secondary outcome was the period from induction to active phase of labor. RESULTS: In the analysis of primiparous pregnants, combination of intracervical Foley balloon catheter and intravaginal PgE2 insertion was shown to be associated with shorter duration from induction to active stage of labor (1000 vs. 585 min, P < 0.001) and also to delivery (1386 vs. 1001 min, P < 0.001). Groups were found to be similar in terms of duration from induction to active stage of labor (670.5 vs. 535.2, P > 0.05) and also to delivery (933.1 vs. 777.9, P > 0.05, Table 2) in subgroup of women with the previous vaginal delivery. CONCLUSIONS: Combined application of intracervical Foley balloon catheter and intravaginal PgE2 insert may result in a shorter time from labor induction to delivery without rising the risk of cesarean section in primiparous women with an unfavorable cervix.

Effect of vaginal washing before intravaginal dinoprostone insertion for labor induction: A randomized clinical trial.

AIM: Prostaglandins have a dual action of cervical ripening and induction of uterine contraction. This study was designed to compare the effectiveness of vaginal washing just before insertion of intravaginal dinoprostone. METHODS: A randomized controlled trial was conducted at the Zeynep Kamil Women and Children's Health Training and Research Hospital. One hundred and ninety-one women with singleton, term pregnancy who underwent labor induction were randomly assigned to two groups: Group 1 consisted of 95 pregnant women with vaginal washing before intravaginal dinoprostone (Propess system for slow release system of 10 mg of dinoprostone) insertion (study group), and 96 pregnant women constituted the control group who did not undergo vaginal washing before intravaginal dinoprostone insertion. A parallel randomized controlled trial was conducted with an allocation ratio of 1:1 to compare the effectiveness of vaginal washing before intravaginal dinoprostone insertion. RESULTS: The groups had similar mean age, body mass index, gestational age, gravidity, parity and Bishop score before agent insertion (P > 0.05). Duration of dinoprostone kept intravaginally, duration from the beginning of dinoprostone insert vaginally to the active phase of labor and duration from the time of intravaginal dinoprostone insertion to delivery were significantly longer in the control group (P < 0.05). Uterine hyperstimulation rate was significantly higher in study group compared to control group (P < 0.05). Meconium passage, fetal infection and neonatal intensive care unit admission were significantly higher in the control group (P < 0.05). CONCLUSION: Vaginal washing before intravaginal dinoprostone insertion may increase Prostaglandin E2 bioavailability as we found shorter duration and better outcome of labor induction in the present study.

A new technique to simplify the minimally invasive parathyroidectomy: Ultrasound-assisted guided wire localization for solitary parathyroid adenomas.

OBJECTIVE: To investigate the benefits of ultrasound-assisted guided wire localization in MIP for selected cases. METHODS: In this prospective, nonrandomised study, we included 36 patients with solitary parathyroid adenomas diagnosed preoperatively by 99m Tc sesta MIBI scintigraphy and/or neck ultrasonography. An ultrasound-guided wire was placed in the solitary parathyroid adenoma preoperatively. MIPs were performed under local anaesthesia plus sedation. After the excision, the parathyroidectomy was confirmed with postoperative ultrasonography. RESULTS: There were 36 patients included in our study. The mean age was 54.89±11.28 years, and 30 patients were females (83.3%). Preoperative PTH and calcium (Ca) levels were 269.5 pg/mL (83.5-5,000 pg/mL) and 12.2 mg/dL (11.1-20 mg/dL), respectively. Postoperative serum PTH and Ca levels were 42.04±26.65 pg/mL and 8.95±0.74 mg/dL, respectively. The mean operation time was 21.69±6.4 minutes and the average hospitalisation time was 18 hours (range: 10-72 hours). CONCLUSIONS: Ultrasound-assisted guided wire localization may be useful in selected MIP cases. The MIP advantages include higher success rates and being easy to learn and practise.

Severe hyperparathyroidism in patient with right thyroid hemiagenesis.

Thyroid hemiagenesis is an infrequent congenital disorder which is rarely associated with hyperparathyroidism. We present a case of an adult woman who presented with hyperparathyroidism and ipsilateral thyroid hemiagenesis. Parathyroid adenoma was excised by minimal invasive parathyroidectomy.

Vaginal micronized progesterone capsule versus vaginal progesterone gel for lutheal support in normoresponder IVF/ICSI-ET cycles.

OBJECTIVE: To compare the outcomes of luteal phase support by micronized progesteron vaginal capsule 600mg/day and progesterone vaginal gel 180mg/day in the normoresponder IVF/ICSI-ET cycles of the patients down-regulated via GnRH agonist long protocol or fixed antagonist protocol below 40 years of age. METHODS: A total of 463 normoresponder cycles between January 2013 and December 2013 were retrospectively analyzed. Those with a BMI>28 kg/m(2), any kind of uterine, ovarian or adnexial pathology, any significant systemic, endocrine or metabolic disease or who were reported as azoospermia, were excluded from the study. The patients were grouped according to the usage of micronized progesterone vaginal capsule 600mg/day (Group 1) or progesterone vaginal gel 180mg/day (Group 2) as luteal phase support. Treatment cycle characteristics and pregnancy outcomes were compared between groups. RESULTS: Group-I included 220 cycles and group 2 included 243 cycles. Although the MII oocyte percentage among the total number of MII oocytes was significantly higher in Group-II (77.5% and 80.2%; p=0.034), positive ß-hCG (32.3% and 21.8%; p=0.015) and clinical pregnancy (27.3% and 17.7%; p=0.018) rates were significantly higher in Group-I. No difference was observed between groups regarding the ongoing pregnancy rates (23.2% and 17.3%; p=0.143). CONCLUSION: Micronized progesterone vaginal capsule 600mg daily used for luteal support in the IVF/ICSI-ET cycles was observed to significantly increase the biochemical and clinical pregnancy rates compared to progesterone vaginal gel 180mg daily. However, no difference was observed between two groups regarding ongoing pregnancy rates.

Aromatase inhibitor treatment for breast cancer: short-term effect on bone health.

AIM OF THIS STUDY: Aim of this study was to examine the effects of aromatase inhibitors (AIs), which are used in every phase of breast cancer treatment, on the bone mineral density (BMD) of patients with early-stage breast cancer. MATERIAL AND METHODS: Menopausal female patients who were diagnosed with stages 1-3 breast cancer and who were planned for anastrazole or letrozole as adjuvant therapy were examined. After the patients' BMD was measured, 45 patients without osteoporosis were included in the study. Six months after AI therapy started, the patients' BMD was measured again. RESULTS: In this study, we tried to show that there was a statistical difference in the BMD of 45 patients before and 6 months after treatment. Among all measurements (femur and lumbar T-scores), the femur Z-score (p = 0.52) was the only score that was not statistically significant. Statistical significance (p < 0.01) was detected in comparative analysis of the other measurements. According to this analysis, a significant loss of BMD was seen even in the first six months after AI treatment was introduced. CONCLUSIONS: Female patients with breast cancer are at higher risk for bone loss and fractures than healthy women. In this study, we showed the negative effects on BMD of aromatase inhibitor therapy, one of the main contributions to osteoporosis in women with breast cancer. This study is the first to quantify the short-term effect of AI treatment on BMD in postmenopausal women with breast cancer.

Crimean-Congo hemorrhagic fever among health care workers, Turkey.

We investigated 9 cases of Crimean-Congo hemorrhagic fever (1 fatal, 2 asymptomatic) among health care workers in Turkey. Needlestick injuries were reported for 4 workers. Eight received ribavirin. In addition to standard precautions, airborne infection isolation precautions are essential during aerosol-generating procedures. For postexposure prophylaxis and therapy, ribavirin should be given.

Emergency peripartum hysterectomy: our 12-year experience.

OBJECTIVE: The aim of this study was to determine the incidence, indications and the risk factors and complications of emergency peripartum hysterectomy (EPH). METHODS: We analyzed retrospectively 44 cases of EPH performed at tertiary obstetric center between January 2001 and April 2013. Data related to demographics, reproductive histories, indications for EPH, and postoperative follow-up were obtained by analyses of hospital records. RESULTS: The overall incidence of EPH was 0.48 per 1,000 deliveries during the study period. The most common indications of EPH were abnormal placentation (50 %), uterine atony (36 %) and uterine rupture (9 %). All patients who underwent EPH with abnormal placentation had one or more previous cesarean sections (CS) except one. In our series, 24 cases (54 %) underwent total hysterectomy, most of which had the diagnosis of abnormal placentation (75 %), whereas subtotal hysterectomy was the choice of management of bleeding in cases with uterine atony (60 %). Maternal mortality was seen in 2 patients (4.5 %). The causes were disseminated intravascular coagulation in one and adult respiratory distress syndrome in the other patient. Perinatal mortality was observed in 7 patients (16 %). The causes for perinatal mortality were placental abruption in 4 and prematurity in 3 patients. CONCLUSIONS: In our series, abnormal placentation was the most common indication for EPH. The risk factors for EPH were previous CS for abnormal placentation and placental abruption for uterine atony and peripartum hemorrhage. Limiting the number of CS deliveries would bring a significant impact on decreasing the risk of EPH.

Severity scoring index for Crimean-Congo hemorrhagic fever and the impact of ribavirin and corticosteroids on fatality.

BACKGROUND: Patients infected with Crimean-Congo hemorrhagic fever (CCHF) virus present with a wide clinical spectrum. In observational studies, the effects of therapeutic agents are confounded by severity. We describe use of a clinical severity scoring index (SSI) for CCHF patients and assess the effect of ribavirin and corticosteroid therapy on the case-fatality rate, stratified by SSI. METHODS: The study group included hospitalized patients who received a diagnosis of CCHF at the Infectious Diseases and Clinical Microbiology Clinic of Ankara Numune Education and Research Hospital between 2004 and 2011. The SSI included platelet count, bleeding, fibrinogen level, activated partial thromboplastin time, and somnolence. The effects of ribavirin and corticosteroid on the case-fatality rate were studied by univariate and multivariate analysis, stratified by SSI. RESULTS: Two hundred eighty-one confirmed cases of CCHF were included in the study. Of 281 patients, 23 (8%) died. The mean age (±SD) of the patients was 47 ± 16 years. Forty-nine percent were female. The mean duration of stay at our clinic after onset of symptoms was 4.4 days, with a range of 1-14 days. In multivariate analysis of factors for the prediction of death, the SSI (odds ratio [OR], 3.27; 95% confidence interval [CI], 2.09-5.13) and ribavirin use (OR, 0.04; 95% CI, .004-.48) were found to be statistically significant factors. CONCLUSION: The SSI is an accurate predictor of death and will therefore be a useful tool for case management and for drug-assessment studies. After stratification of cases by SSI, ribavirin was found to be effective in reducing the case-fatality rate, especially among moderately ill patients, whereas steroids were found to be beneficial particularly among patients with severe disease.

Smooth muscle tumor of uncertain malignant potential (STUMP): a case-based analysis.

OBJECTIVES: The present study aimed to analyze of uterine smooth muscle tumors of uncertain malignant potential (STUMP) and the outcomes of patients with STUMP. MATERIAL AND METHODS: In this retrospective study, the data of patients diagnosed with STUMP in a single tertiary center between January 2005-January 2020 were reviewed. We assessed the demographic variables, treatment outcomes, time until recurrence, disease-free and overall survival of the patients. RESULTS: Twenty-five patients diagnosed with STUMP were included in the study. The mean age of the patients was 43.2 ± 10.3 years. Thirteen of the 25 patients (52%) were treated by myomectomy, others received diagnoses following hysterectomy. The median follow-up time was 45.2 months. Recurrence was observed in three cases (12%), two of which were followed up without hysterectomy, and the third patient died by peritonitis carcinomatosa 60 months after diagnosis although she received cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) treatment. CONCLUSIONS: This study evaluates the data of patients with STUMP. Our results reveal a STUMP recurrence of 12%, like those previously reported in the literature. Despite the possibility of malignant recurrence, fertility-preserving treatment with close follow-up should be tried, because of the relatively early age at diagnosis.

Subacute THYROiditis Related to SARS-CoV-2 VAccine and Covid-19 (THYROVAC Study): A Multicenter Nationwide Study.

CONTEXT: The aims of the study are to compare characteristics of subacute thyroiditis (SAT) related to different etiologies, and to identify predictors of recurrence of SAT and incident hypothyroidism. METHODS: This nationwide, multicenter, retrospective cohort study included 53 endocrinology centers in Turkey. The study participants were divided into either COVID-19-related SAT (Cov-SAT), SARS-CoV-2 vaccine-related SAT (Vac-SAT), or control SAT (Cont-SAT) groups. RESULTS: Of the 811 patients, 258 (31.8%) were included in the Vac-SAT group, 98 (12.1%) in the Cov-SAT group, and 455 (56.1%) in the Cont-SAT group. No difference was found between the groups with regard to laboratory and imaging findings. SAT etiology was not an independent predictor of recurrence or hypothyroidism. In the entire cohort, steroid therapy requirement and younger age were statistically significant predictors for SAT recurrence. C-reactive protein measured during SAT onset, female sex, absence of antithyroid peroxidase (TPO) positivity, and absence of steroid therapy were statistically significant predictors of incident (early) hypothyroidism, irrespective of SAT etiology. On the other hand, probable predictors of established hypothyroidism differed from that of incident hypothyroidism. CONCLUSION: Since there is no difference in terms of follow-up parameters and outcomes, COVID-19- and SARS-CoV-2 vaccine-related SAT can be treated and followed up like classic SATs. Recurrence was determined by younger age and steroid therapy requirement. Steroid therapy independently predicts incident hypothyroidism that may sometimes be transient in overall SAT and is also associated with a lower risk of established hypothyroidism.

Serum levels of omentin in end-stage renal disease patients.

INTRODUCTION: Cardiovascular disease is the leading cause of morbidity and mortality in hemodialysis patients. Therefore, evaluation and prevention of cardiovascular diseases in end-stage renal disease (ESRD) patients are very important. The plasma level of omentin was found to be associated with different conditions such as insulin resistance. It is one of the novel adipokines synthesized mainly in the visceral adipose tissue. In this study, we aimed to investigate the level of omentin in patients with ESRD receiving hemodialysis. METHODS: The study population consisted of 59 adult chronic hemodialysis patients (30 women and 29 men) and age-matched control subjects were selected from apparently healthy subjects (28 participants; 14 women and 14 men). Blood samples were obtained before the dialysis session. Omentin concentrations were determined by using enzyme-linked immunosorbent assay. RESULTS: Plasma levels of omentin were found to be markedly higher in ESRD patients (606.6 ± 313.0 ng/ml) than in the control group (357.5 ± 147.4 ng/ml; p < 0.0001). Also, serum omentin levels were found to be correlated with creatinine (r = 0.333, p = 0.002). CONCLUSIONS: Omentin levels were found to be elevated in patients with ESRD receiving hemodialysis. To the best of our knowledge, this is the first clinical study that demonstrated the association between omentin and ESRD.

A Case of Thyroid Follicular Carcinoma Presented with Skin Metastasis.

Skin metastases due to thyroid carcinomas are extremely rare and represent advanced disease and poor prognosis. Diagnosing a skin nodule, which may appear as the first clinical symptom of latent malignancy with low metastatic potential, is likely to be challenging. Distant metastases of thyroid carcinomas need to be identified accurately and quickly; late diagnosis and treatment will lead to increased mortality in patients. A case of thyroid follicular carcinoma presenting with skin metastasis is very rare. Herein, we present a case of a nodular skin lesion in the left lumbar region of a 66-year female due to thyroid follicular carcinoma metastasis and discuss it in the light of existing literature. Key Words: Follicular thyroid carcinoma, Pulmonary nodule, Metastasis, skin.

Increased maternal leptin levels may be an indicator of subclinical hypothyroidism in a newborn.

Background: Several factors may influence newborn thyroid-stimulating hormone (TSH) concentrations and cause subclinical hypothyroidism in a newborn. A sufficient level of leptin signalling is needed for the normal production of TSH and thyroid hormones by the thyroid gland. Our study aimed to investigate the correlation between maternal serum leptin concentration during the third trimester of pregnancy and newborn screening-TSH levels. Methods: This prospective cross-sectional study was conducted in obstetrics and gynaecology clinics of a state hospital between June and August 2013. Maternal venous blood samples were collected from 270 healthy pregnant women in the third trimester just before delivery. Measurements of maternal fT3, fT4, TSH, anti-thyroid peroxidase (TPO), and anti-thyroglobulin (anti-Tg) antibodies from serum samples were performed by chemiluminescence immunoassay. Maternal serum leptin levels were determined by ELISA. Dried capillary blood spots were used to measure newborn TSH levels. Results: Subjects were divided into two groups according to the neonatal TSH levels using a cut-point of 5.5 mIU/L. Median maternal serum leptin levels were significantly higher in newborns whose TSH levels were higher than >5.5 mIU/L [13.2 µg/L (1.3 - 46.5) vs 19.7 µg/L (2.4 - 48.5), p<0.05]. Serum leptin levels showed a negative correlation with maternal fT4 (r=0.32, p<0.05), fT3 (r=0.23, p<0.05), and a positive correlation with BMI (r=0.30, p<0.05). Conclusions: Our results suggest that high leptin levels in the third trimester of pregnancy influence maternal thyroid functions and might cause an increase in newborn TSH levels. Detection of high maternal serum leptin levels may be a reason for subclinical hypothyroidism.

Biochemical characteristics and calcium and PTH levels of patients with high normal and elevated serum 25(OH)D levels in Turkey: DeVIT-TOX survey.

Vitamin D intake over the recommended dose is usually associated with high serum 25(OH)D levels and generally not associated with symptoms of hypercalcemia. High doses of cholecalciferol need to be avoided to protect against vitamin D toxicity and related complications. Strict adherence to the clinical guidelines for treating vitamin D deficiency can ensure safe and effective treatment. PURPOSE: We observed a tendency to use high doses of cholecalciferol for vitamin D deficiency treatment or vitamin D supplementation. We aimed to determine the biochemical characteristics of patients with high normal and elevated serum 25(OH)D levels. METHODS: An online invitation was sent to all tertiary endocrinology clinics in Turkey to complete an online retrospective survey (DeVIT-TOX Survey) for patients diagnosed with high serum 25(OH)D levels (> 88 ng/mL) between January 2019 and December 2019. The patients were evaluated according to the presence of signs and symptoms of hypercalcemia and doses of vitamin D intake, evaluated into the following three groups according to their 25(OH)D levels: group 1, > 150 ng/mL; group 2, 149-100 ng/mL; and group 3, 99-88 ng/mL. RESULTS: A total of 253 patients were included in the final analysis (female/male: 215/38; mean age, 51.5 ± 15.6 years). The average serum 25(OH)D level was 119.9 ± 33 (range, 88-455) ng/mL, and the average serum calcium level was 9.8 ± 0.7 (range, 8.1-13.1) mg/dL. Most (n = 201; 75.4%) patients were asymptomatic despite having high serum 25(OH)D and calcium levels. The serum 25(OH)D level was significantly higher in the symptomatic groups than in the asymptomatic groups (138.6 ± 64 ng/mL vs. 117.7 ± 31 ng/mL, p < 0.05). The most common cause (73.5%) associated with high serum 25(OH)D levels was the inappropriate prescription of a high dose of oral vitamin D (600.000-1.500.000 IU) for treating vitamin D deficiency/insufficiency in a short time (1-3 months). The cut-off value of 25 (OH) D level in patients with hypercalcemia was found to be 89 ng/mL [median 116.5 (89-216)]. CONCLUSIONS: High dose of vitamin D intake is associated with a high serum 25 OH D level, without symptoms of hypercalcemia. Inappropriate prescription of vitamin D is the primary cause for elevated 25(OH) D levels and related hypercalcemia. Hypercalcemia may not be observed in every patient at very high 25(OH) D levels. Adherence to the recommendation of guidelines is essential to ensure safe and effective treatment of vitamin D deficiency.

Distinct conformations of the HIV-1 V3 loop crown are targetable for broad neutralization.

The V3 loop of the HIV-1 envelope (Env) protein elicits a vigorous, but largely non-neutralizing antibody response directed to the V3-crown, whereas rare broadly neutralizing antibodies (bnAbs) target the V3-base. Challenging this view, we present V3-crown directed broadly neutralizing Designed Ankyrin Repeat Proteins (bnDs) matching the breadth of V3-base bnAbs. While most bnAbs target prefusion Env, V3-crown bnDs bind open Env conformations triggered by CD4 engagement. BnDs achieve breadth by focusing on highly conserved residues that are accessible in two distinct V3 conformations, one of which resembles CCR5-bound V3. We further show that these V3-crown conformations can, in principle, be attacked by antibodies. Supporting this conclusion, analysis of antibody binding activity in the Swiss 4.5 K HIV-1 cohort (n = 4,281) revealed a co-evolution of V3-crown reactivities and neutralization breadth. Our results indicate a role of V3-crown responses and its conformational preferences in bnAb development to be considered in preventive and therapeutic approaches.

Evaluation of circulating cell free DNA in plasma as a biomarker of different thyroid diseases.

INTRODUCTION: Many studies have been done on proteomics, genomics, epigenetic, immunogenetics in many body fluids. Among these, circulating cell-free DNA (ccfDNA) entered the literature in 1948, but it has not been studied for many years due to technological deficiencies. Following recent advances, geno-metastasis has been mentioned and new research is needed in this area. ccfDNA is known to be an important biomolecule in this regard. OBJECTIVE: The presence of cell-free DNA in the circulatory system may offer a tremendous opportunity to provide novel biomarkers for thyroid diseases. This experimental study was conducted to determine the amount of ccfDNA in different thyroid diseases, then to evaluate whether the ccfDNA concentration varied between the disease groups and control group. METHODS: In total, we included 121 individuals in the present study. We collected blood samples and then determined the ccfDNA concentration in plasma of collected blood samples from three groups: thyroiditis (n=33), benign (n=37), and malignant (n=30) and from a control group (n=21). RESULTS: The median values of the ccfDNA groups were found as 1610, 1665, 1685 and 576ng/mL for the thyroiditis, benign, malign, and control groups, respectively. Findings showed that the ccfDNA of the three groups was significantly higher than the control (p<0.0001). Each group was compared in terms of ccfDNA and the p-values of benign-thyroiditis, benign-malign, and thyroiditis-malign were 0.09, 0.65, and 0.29, respectively. CONCLUSIONS: The clear differences between thyroid diseases and controls suggest that ccfDNA is worthy of attention as a biomarker for further evaluation of different thyroid diseases. Likewise, it might indicate a clear tendency that ccfDNA can also be used to distinguish different thyroid diseases.

Continuous oxytocin versus intermittent oxytocin for induction of labor: a randomized study.

Objective: To assess whether intermittent usage of oxytocin infusion increases the duration of the active phase of labor and reduces maternal and neonatal complications or not.Materials and Methods: A prospective randomized controlled study was conducted of 200 consenting women with singleton pregnancy in the vertex position undergoing labor induction or augmentation at the Zeynep Kamil Maternity and Children's Training and Research Hospital. Participants with cervical dilation of 3 cm were randomized to either continued or intermittent oxytocin infusion when cervical dilation reached 5 cm. The primary outcome measures were the duration of the active phase of labor, defined as the period of labor from 5 cm of cervical dilation to vaginal delivery. Secondary outcomes were the duration of oxytocin infusion, mode of delivery, hyperstimulation, abnormalities in fetal heart rate, perineal tears, and neonatal outcomes.Results: The median duration of the active phase for the women with a vaginal delivery was longer in the intermittent oxytocin group than the continued oxytocin group, but it was not statistically significant (median, 6.91 vs. 7.58 h, p = .37). There was a significant difference in the duration of oxytocin infusion (median, 12.38 h in the intermittent group vs. 15.79 h in the continued group, p = .005). The incidence of uterine hyperstimulation was significantly greater in the continued group (21.1%) than the intermittent oxytocin group (3.8%) (p=.001).Conclusions: Intermittent usage of oxytocin infusion seems to make labor less complicated without lengthening duration of labor.