Imaging in gynecological disease: clinical and ultrasound characteristics of intramural pregnancy

OBJECTIVE: To describe the clinical and sonographic characteristics of intramural pregnancies, the available management options and treatment outcomes. METHODS: This was a retrospective single-center study of consecutive patients diagnosed by ultrasound with an intramural pregnancy, between 2008 and 2022. An intramural pregnancy was diagnosed on ultrasound examination when a pregnancy located within the confines of the uterus, extended beyond the decidual-myometrial junction to involve the myometrium above the level of the internal cervical os. Clinical, ultrasound, relevant surgical and histological information and outcomes were retrieved from each patient's record. RESULTS: Eighteen patients diagnosed with an intramural pregnancy were identified. Median age was 35 (range, 28-43) years. Median gestational age was 8+1 (range, 5+5 - 12+0 ) weeks. Vaginal bleeding with or without abdominal pain was the most common presenting symptom, which was recorded in 8/18 (44%) of patients. 9/18 (50%) of patients had partial and 9/18 (50%) complete intramural pregnancies. Embryonic cardiac activity was present in 8/18 (44%) of pregnancies. The majority of pregnancies [10/18 (56%)] were initially managed conservatively, including expectant management [8/18 (44%)], local injection of methotrexate [1/18 (6%)] and embryocide [1/18 (6%)]. Conservative management was successful in 9/10 (90%) of women with a median hCG resolution time of 71 (range, 32-143) days and median pregnancy resolution time of 63 (range, 45-214) days. One patient with an ongoing live pregnancy had an emergency hysterectomy for a major vaginal bleed at 20 weeks' gestation. No other patients who were managed conservatively experienced any significant complications. The remaining 8/18 (44%) patients had primary surgical treatment, which was mainly in the form of transcervical suction curettage [7/8 (88%)] whist the remaining patient presented with uterine rupture and had an emergency laparoscopy and repair. CONCLUSIONS: We describe the ultrasound features for partial and complete intramural pregnancies with demonstration of key diagnostic features. Our series suggest that when intramural pregnancies are diagnosed before 12 weeks' of gestational age they can be managed with either conservative or surgical treatment, with most women being able to preserve their future reproductive function. This article is protected by copyright. All rights reserved

A family of E. coli expression vectors for laboratory scale and high throughput soluble protein production

BACKGROUND: In the past few years, both automated and manual high-throughput protein expression and purification has become an accessible means to rapidly screen and produce soluble proteins for structural and functional studies. However, many of the commercial vectors encoding different solubility tags require different cloning and purification steps for each vector, considerably slowing down expression screening. We have developed a set of E. coli expression vectors with different solubility tags that allow for parallel cloning from a single PCR product and can be purified using the same protocol. RESULTS: The set of E. coli expression vectors, encode for either a hexa-histidine tag or the three most commonly used solubility tags (GST, MBP, NusA) and all with an N-terminal hexa-histidine sequence. The result is two-fold: the His-tag facilitates purification by immobilised metal affinity chromatography, whilst the fusion domains act primarily as solubility aids during expression, in addition to providing an optional purification step. We have also incorporated a TEV recognition sequence following the solubility tag domain, which allows for highly specific cleavage (using TEV protease) of the fusion protein to yield native protein. These vectors are also designed for ligation-independent cloning and they possess a high-level expressing T7 promoter, which is suitable for auto-induction. To validate our vector system, we have cloned four different genes and also one gene into all four vectors and used small-scale expression and purification techniques. We demonstrate that the vectors are capable of high levels of expression and that efficient screening of new proteins can be readily achieved at the laboratory level. CONCLUSION: The result is a set of four rationally designed vectors, which can be used for streamlined cloning, expression and purification of target proteins in the laboratory and have the potential for being adaptable to a high-throughput screening

Simulation of the Melting Behavior of the UO2-Zircaloy Fuel Cladding System by Laser Heating

The current research focuses on laser melting and successive analysis of laboratory-scale uranium dioxide nuclear fuel samples in direct contact with Zircaloy-4 cladding. The goal was to characterize the melted and refrozen interfaces, in particular, observing local changes of the melting point and interdiffusion of fuel and cladding materials under inert gas (Ar), in the presence of hydrogen (Ar + 6% H2) or in air. Results obtained by laser heating UO2 pellets clad in a Zircaloy ring were interpreted in light of reference tests performed on pellets in which UO2 and zirconium were blended in a series of given compositions. The sample composition was analyzed by scanning electron microscopy to verify the occurrence of diffusion and segregation phenomena during the laser-heating cycles. Laser-melting experiments were performed on pellets of uranium dioxide clad in Zircaloy-4 rings to simulate the configuration of a light water reactor fuel rod. Under inert gas, the material interdiffusion resulted in consistent melting point depression (of up to 200 K below the melting point of pure UO2) at the interface between the fuel and the cladding. Experiments carried out in the presence of H2 displayed a more limited effect on the melting temperature, but they resulted in a remarkable embrittlement of the whole structure, with large fragmentation of the Zircaloy cladding. This was probably due to the formation of brittle and highly volatile Zr hydrides. The observed melting point decrease was even more pronounced (up to over 400 K) under air in uranium-rich samples, due to the change in the stoichiometry of UO2 in UO2+x

Intra- and interobserver reproducibility of pelvic ultrasound for the detection and measurement of endometriotic lesions

STUDY QUESTION: What is the interobserver and intraobserver reproducibility of pelvic ultrasound for the detection of endometriotic lesions? SUMMARY ANSWER: Pelvic ultrasound is highly reproducible for the detection of pelvic endometriotic lesions. WHAT IS KNOWN ALREADY: Transvaginal ultrasound (TVS) has been widely adopted as the first-line assessment for the diagnosis and assessment of pelvic endometriosis. Severity of endometriosis as assessed by ultrasound has been shown to have good concordance with laparoscopy (kappa 0.79). The reproducibility of TVS for assessment of ovarian mobility and pouch of Douglas obliteration using the 'sliding sign' has already been described in the literature. However, there is no available data in the literature to demonstrate the intraobserver repeatability of measurements for endometriotic cysts and nodules. STUDY DESIGN SIZE DURATION: This was a prospective observational cross-sectional study conducted over a period of 12 months. We included 50 consecutive women who were all examined by two operators (A and B) during their clinic attendance. PARTICIPANTS/MATERIALS SETTING METHODS: The study was carried out in a specialist endometriosis centre. We included all consecutive women who had ultrasound scans performed independently by two experienced operators during the same visit to the clinic. The outcomes of interest were the inter- and intraobserver reproducibility for the detection of endometriotic lesions. We also assessed repeatability of the measurements of lesion size. MAIN RESULTS AND THE ROLE OF CHANCE: There was a good level of agreement between operator A and operator B in detecting the presence of pelvic endometriotic lesions (k = 0.72). There was a very good level of agreement between operators in identifying endometriotic cysts (k = 0.88) and a good level of agreement in identifying endometriotic nodules (k = 0.61). The inter- and intraobserver repeatability of measuring endometriotic cysts was excellent (intra-class correlation (ICC) ≥ 0.98). There was good interobserver measurement repeatability for bowel nodules (ICC 0.88), but the results for nodules in the posterior compartment were poor (ICC 0.41). The intraobserver repeatability for nodule size measurements was good for both operators (ICC ≥0.86). LIMITATIONS REASONS FOR CAUTION: Within this cohort, there was insufficient data to perform a separate analysis for nodule size in the anterior compartment. All examinations were performed within a specialised unit with a high prevalence of deep endometriosis. Our findings may not apply to operators without intensive ultrasound training in the diagnosis of pelvic endometriosis. WIDER IMPLICATIONS OF THE FINDINGS: These findings are important because ultrasound has been widely accepted as the first-line investigation for the diagnosis of pelvic endometriosis, which often determines the need for future investigations and treatment. The detection and measurement of bowel nodules is essential for anticipation of surgical risk and planning surgical excision. STUDY FUNDING/COMPETING INTERESTS: The authors have no conflict of interest. No funding was obtained for this work

Pneumococcal conjugate vaccine dose-ranging studies in humans: A systematic review

Background: Streptococcus pneumoniae is one of the most common bacterial pathogens of infants and young children. Antibody responses against the pneumococcal polysaccharide capsule are the basis of vaccine-mediated protection. We examined the relationship between the dose of polysaccharide in pneumococcal conjugate vaccines (PCVs) and immunogenicity. Methods: A systematic search of English publications that evaluated the immunogenicity of varying doses of pneumococcal conjugate vaccines was performed in Medline and Embase (Ovid Sp) databases in August 2019. We included only articles that involved administration of pneumococcal conjugate vaccine in humans and assessed the immunogenicity of more than one serotype-specific saccharide dose. Results were synthesised descriptively due to the heterogeneity of product valency, product content and vaccine schedule. Results: We identified 1691 articles after de-duplication; 9 studies met our inclusion criteria; 2 in adults, 6 in children and 1 in both. Doses of polysaccharide evaluated ranged from 0.44 mcg to 17.6 mcg. In infants, all doses tested elicited IgG geometric mean concentrations (GMCs) above the established correlate of protection (COP; 0.35 mcg/ml). A month after completion of the administered vaccine schedule, 95% confidence intervals of only three out of all the doses evaluated had GMCs that crossed below the COP. In the adult studies, all adults achieved GMCs that would be considered protective in children who have received 3 standard vaccine doses. Conclusion: For some products, the mean antibody concentrations induced against some pneumococcal serotypes increased with increasing doses of the polysaccharide conjugate, but for other serotypes, there were no clear dose–response relationships or the dose response curves were negative. Fractional doses of polysaccharide which contain less than is included in currently distributed formulations may be useful in the development of higher valency vaccines, or dose-sparing delivery for paediatric use

Effect of two different house screening interventions on exposure to malaria vectors and on anaemia in children in The Gambia: a randomised controlled trial

Background: House screening should protect people against malaria. We assessed whether two types of house screening—full screening of windows, doors, and closing eaves, or installation of screened ceilings—could reduce house entry of malaria vectors and frequency of anaemia in children in an area of seasonal malaria transmission. Methods: During 2006 and 2007, 500 occupied houses in and near Farafenni town in The Gambia, an area with low use of insecticide-treated bednets, were randomly assigned to receive full screening, screened ceilings, or no screening (control). Randomisation was done by computer-generated list, in permuted blocks of five houses in the ratio 2:2:1. Screening was not treated with insecticide. Exposure to mosquitoes indoors was assessed by fortnightly light trap collections during the transmission season. Primary endpoints included the number of female Anopheles gambiae sensu lato mosquitoes collected per trap per night. Secondary endpoints included frequency of anaemia (haemoglobin concentration <80 g/L) and parasitaemia at the end of the transmission season in children (aged 6 months to 10 years) who were living in the study houses. Analysis was by modified intention to treat (ITT), including all randomised houses for which there were some outcome data and all children from those houses who were sampled for haemoglobin and parasitaemia. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN51184253. Findings: 462 houses were included in the modified ITT analysis (full screening, n=188; screened ceilings, n=178; control, n=96). The mean number of A gambiae caught in houses without screening was 37·5 per trap per night (95% CI 31·6–43·3), compared with 15·2 (12·9–17·4) in houses with full screening (ratio of means 0·41, 95% CI 0·31–0·54; p<0·0001) and 19·1 (16·1–22·1) in houses with screened ceilings (ratio 0·53, 0·40–0·70; p<0·0001). 755 children completed the study, of whom 731 had complete clinical and covariate data and were used in the analysis of clinical outcomes. 30 (19%) of 158 children from control houses had anaemia, compared with 38 (12%) of 309 from houses with full screening (adjusted odds ratio [OR] 0·53, 95% CI 0·29–0·97; p=0·04), and 31 (12%) of 264 from houses with screened ceilings (OR 0·51, 0·27–0·96; p=0·04). Frequency of parasitaemia did not differ between intervention and control groups. Interpretation: House screening substantially reduced the number of mosquitoes inside houses and could contribute to prevention of anaemia in children