Cervical dilatation and preparation prior to outpatient hysteroscopy: a systematic review and meta-analysis.

BACKGROUND: There are uncertainties about the benefit of routine cervical preparation and/or cervical dilatation before outpatient hysteroscopy. OBJECTIVE: To determine if cervical preparation and/or routine mechanical dilatation reduces pain during outpatient hysteroscopy. SEARCH STRATEGY: MEDLINE, EMBASE, CINAHL and CENTRAL were searched on 19 October 2020, using keywords 'hysteroscopy', 'cervical preparation', 'cervical ripening', 'cervical dilatation', 'outpatient', 'office' and/or 'ambulatory' and associated medical subject headings. SELECTION CRITERIA: Randomised controlled trials investigating the benefit of cervical preparation and/or cervical dilatation on pain in women undergoing outpatient hysteroscopy were included. DATA COLLECTION AND ANALYSIS: Two independent reviewers selected eligible trials and extracted data on pain, feasibility, adverse events and satisfaction/acceptability for meta-analysis. MAIN RESULTS: The literature search yielded 807 records, of which 24 were included for review and 19 provided data for meta-analysis. No trials investigated the role of routine mechanical cervical dilatation. Cervical preparation significantly reduced pain during outpatient hysteroscopy; standard mean difference (SMD) -0.67, 95% confidence interval (CI) -1.05 to -0.29. Feasibility also improved as priming provided significantly easier hysteroscopic entry (SMD 0.89, 95% CI 0.32-1.46), greater cervical dilatation (SMD 0.81, 95% CI 0.08-1.53) and shorter procedural times (SMD -0.51, 95% CI -0.88 to -0.13). Cervical preparation, however, incurred significantly more adverse effects, mainly comprising genital tract bleeding, abdominal pain and gastrointestinal symptoms (odds ratio 2.94, 95% CI 1.58-5.47). There were limited data regarding satisfaction, acceptability and complications. CONCLUSIONS: Cervical preparation reduces pain and improves feasibility associated with outpatient hysteroscopy but increases the risk of adverse effects. TWEETABLE ABSTRACT: Cervical preparation before outpatient hysteroscopy reduces pain, enhances feasibility but increases adverse effects.

Vaginoscopy Against Standard Treatment: a randomised controlled trial.

OBJECTIVE: To evaluate whether vaginoscopy or standard hysteroscopy was more successful in the outpatient setting. DESIGN: Randomised controlled multicentre trial. SETTING: Outpatient hysteroscopy clinics at two UK hospitals. POPULATION: 1597 women aged 16 or older undergoing an outpatient hysteroscopy. METHODS: Women were allocated to vaginoscopy or standard hysteroscopy using third party randomisation stratified by menopausal status with no blinding of participants or clinicians. MAIN OUTCOME MEASURES: The primary outcome was 'success', a composite endpoint defined as: a complete procedure, no complications, a level of pain acceptable to the patient, and no sign of genitourinary tract infection 2 weeks after the procedure. RESULTS: Vaginoscopy was significantly more successful than standard hysteroscopy [647/726 (89%) versus 621/734 (85%), respectively; relative risk (RR) 1.05, 95% CI 1.01-1.10; P = 0.01]. The median time taken to complete vaginoscopy was 2 minutes compared with 3 minutes for standard hysteroscopy (P < 0.001). The mean pain score was 42.7 for vaginoscopy, which was significantly less than standard hysteroscopy 46.4 (P = 0.02). Operative complications occurred in five women receiving vaginoscopy and 19 women receiving standard hysteroscopy (RR 0.26, 95% CI 0.10-0.69). CONCLUSIONS: Vaginoscopy is quicker to perform, less painful, and more successful than standard hysteroscopy and therefore should be considered the technique of choice for outpatient hysteroscopy. TWEETABLE ABSTRACT: Vaginoscopy is quicker to perform, less painful, and more successful than standard hysteroscopy.

Outcomes in prevention and management of miscarriage trials: a systematic review.

BACKGROUND: There is a substantial body of research evaluating ways to prevent and manage miscarriage, but all studies do not report on the same outcomes. OBJECTIVE: To review systematically, outcomes reported in existing miscarriage trials. SEARCH STRATEGY: MEDLINE, Embase, CINAHL, and Cochrane were searched from inception until January 2017. SELECTION CRITERIA: Randomised controlled trials (RCTs) reporting prevention or management of miscarriage. Miscarriage was defined as a pregnancy loss in the first trimester. DATA COLLECTION AND ANALYSIS: Data about the study characteristics, primary, and secondary outcomes were extracted. MAIN RESULTS: We retrieved 1553 titles and abstracts, from which 208 RCTs were included. For prevention of miscarriage, the most commonly reported primary outcome was live birth and the top four reported outcomes were pregnancy loss/stillbirth (n = 112), gestation of birth (n = 68), birth dimensions (n = 65), and live birth (n = 49). For these four outcomes, 58 specific measures were used for evaluation. For management of miscarriage, the most commonly reported primary outcome was efficacy of treatment. The top four reported outcomes were bleeding (n = 186), efficacy of miscarriage treatment (n = 105), infection (n = 97), and quality of life (n = 90). For these outcomes, 130 specific measures were used for evaluation. CONCLUSIONS: Our review found considerable variation in the reporting of primary and secondary outcomes along with the measures used to assess them. There is a need for standardised patient-centred clinical outcomes through the development of a core outcome set; the work from this systematic review will form the foundation of the core outcome set for miscarriage. TWEETABLE ABSTRACT: There is disparity in the reporting of outcomes and the measures used to assess them in miscarriage trials.

Predicting the chance of live birth for women undergoing IVF: a novel pretreatment counselling tool.

STUDY QUESTION: Which pretreatment patient variables have an effect on live birth rates following assisted conception? SUMMARY ANSWER: The predictors in the final multivariate logistic regression model found to be significantly associated with reduced chances of IVF/ICSI success were increasing age (particularly above 36 years), tubal factor infertility, unexplained infertility and Asian or Black ethnicity. WHAT IS KNOWN ALREADY: The two most widely recognized prediction models for live birth following IVF were developed on data from 1991 to 2007; pre-dating significant changes in clinical practice. These existing IVF outcome prediction models do not incorporate key pretreatment predictors, such as BMI, ethnicity and ovarian reserve, which are readily available now. STUDY DESIGN, SIZE, DURATION: In this cohort study a model to predict live birth was derived using data collected from 9915 women who underwent IVF/ICSI treatment at any CARE (Centres for Assisted Reproduction) clinic from 2008 to 2012. Model validation was performed on data collected from 2723 women who underwent treatment in 2013. The primary outcome for the model was live birth, which was defined as any birth event in which at least one baby was born alive and survived for more than 1 month. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data were collected from 12 fertility clinics within the CARE consortium in the UK. Multivariable logistic regression was used to develop the model. Discriminatory ability was assessed using the area under receiver operating characteristic (AUROC) curve, and calibration was assessed using calibration-in-the-large and the calibration slope test. MAIN RESULTS AND THE ROLE OF CHANCE: The predictors in the final model were female age, BMI, ethnicity, antral follicle count (AFC), previous live birth, previous miscarriage, cause and duration of infertility. Upon assessing predictive ability, the AUROC curve for the final model and validation cohort was (0.62; 95% confidence interval (CI) 0.61-0.63) and (0.62; 95% CI 0.60-0.64) respectively. Calibration-in-the-large showed a systematic over-estimation of the predicted probability of live birth (Intercept (95% CI) = -0.168 (-0.252 to -0.084), P < 0.001). However, the calibration slope test was not significant (slope (95% CI) = 1.129 (0.893-1.365), P = 0.28). Due to the calibration-in-the-large test being significant we recalibrated the final model. The recalibrated model showed a much-improved calibration. LIMITATIONS, REASONS FOR CAUTION: Our model is unable to account for factors such as smoking and alcohol that can affect IVF/ICSI outcome and is somewhat restricted to representing the ethnic distribution and outcomes for the UK population only. We were unable to account for socioeconomic status and it may be that by having 75% of the population paying privately for their treatment, the results cannot be generalized to people of all socioeconomic backgrounds. In addition, patients and clinicians should understand this model is designed for use before treatment begins and does not include variables that become available (oocyte, embryo and endometrial) as treatment progresses. Finally, this model is also limited to use prior to first cycle only. WIDER IMPLICATIONS OF THE FINDINGS: To our knowledge, this is the first study to present a novel, up-to-date model encompassing three readily available prognostic factors; female BMI, ovarian reserve and ethnicity, which have not previously been used in prediction models for IVF outcome. Following geographical validation, the model can be used to build a user-friendly interface to aid decision-making for couples and their clinicians. Thereafter, a feasibility study of its implementation could focus on patient acceptability and quality of decision-making. STUDY FUNDING/COMPETING INTEREST: None.

Global Genome Biodiversity Network: saving a blueprint of the Tree of Life - a botanical perspective.

BACKGROUND: Genomic research depends upon access to DNA or tissue collected and preserved according to high-quality standards. At present, the collections in most natural history museums do not sufficiently address these standards, making them often hard or impossible to use for whole-genome sequencing or transcriptomics. In response to these challenges, natural history museums, herbaria, botanical gardens and other stakeholders have started to build high-quality biodiversity biobanks. Unfortunately, information about these collections remains fragmented, scattered and largely inaccessible. Without a central registry or even an overview of relevant institutions, it is difficult and time-consuming to locate the needed samples. SCOPE: The Global Genome Biodiversity Network (GGBN) was created to fill this vacuum by establishing a one-stop access point for locating samples meeting quality standards for genome-scale applications, while complying with national and international legislations and conventions. Increased accessibility to genomic samples will further genomic research and development, conserve genetic resources, help train the next generation of genome researchers and raise the visibility of biodiversity collections. Additionally, the availability of a data-sharing platform will facilitate identification of gaps in the collections, thereby empowering targeted sampling efforts, increasing the breadth and depth of preservation of genetic diversity. The GGBN is rapidly growing and currently has 41 members. The GGBN covers all branches of the Tree of Life, except humans, but here the focus is on a pilot project with emphasis on 'harvesting' the Tree of Life for vascular plant taxa to enable genome-level studies. CONCLUSION: While current efforts are centred on getting the existing samples of all GGBN members online, a pilot project, GGI-Gardens, has been launched as proof of concept. Over the next 6 years GGI-Gardens aims to add to the GGBN high-quality genetic material from at least one species from each of the approx. 460 vascular plant families and one species from half of the approx. 15 000 vascular plant genera.

Carbyne forms of carbon: do they exist?

Almost 15 years have passed since carbynes entered the literature as new forms of elemental carbon. They recently attracted attention as possible interstellar dust constituents and as carriers of presolar noble gases in meteorites. Their existence and that of the related mineral chaoite are questioned, and a reevaluation of previous data is suggested.

Graphitic carbon in the Allende meteorite: a microstructural study.

High-resolution transmission electron microscopy, shows that carbon in the Allende carbonaceous chondrite meteorite is predominantly a poorly crystalline graphite. Such material is of interest as an important carrier of the isotopically anomalous noble gases found in carbonaceous chondrites.

Dilemmas in Management of the Geriatric Bladder.

PURPOSE OF REVIEW: In this article, we will review current dilemmas regarding evaluation and management of the geriatric bladder incorporating concepts of normal changes of aging as well as common lower urinary tract dysfunction. RECENT FINDINGS: Increasing age leads to functional changes in essentially all organ systems including the genitourinary system. Understanding the natural changes with age of the bladder as well as the signs and symptoms of pathologic conditions is paramount to diagnosis and treatment of urologic conditions in the geriatric population. SUMMARY: There are several conundrums in the diagnosis and evaluation of the geriatric bladder including the ability of the bladder to store, empty, as well as sensitivity disturbances. Diagnostic testing and goals of treatment should be individualized for each patient and personalized to consider patient comorbidities, limitations, and expectations.

The role of angiogenic and wound repair factors during CMV-accelerated transplant vascular sclerosis in rat cardiac transplants.

Human cytomegalovirus (HCMV) accelerates transplant vascular sclerosis (TVS), a consequence of angiogenesis (AG) and wound repair (WR). While HCMV can be localized to TVS lesions, the low number of infected cells suggests a global effect on target tissues. We used microarray analysis followed by real-time-polymerase chain reaction (RT-PCR) in an RCMV-accelerated TVS rat cardiac transplant model to determine whether CMV activates host WR and AG factors. Dysregulated cellular genes in allografts from RCMV-infected recipients were compared to those from uninfected recipients and native hearts. We demonstrated that RCMV upregulates the genes involved in WR and AG, which was highest during the critical time of TVS acceleration (21-28 days). Using a standard in vitro AG assay, virus and serum-free supernatants collected at 48 h postinfection significantly induced endothelial cell (EC) migration, branching and tubule formation compared to supernatants from mock-infected cells. Supernatants from ultraviolet (UV)-inactivated RCMV-infected cells failed to induce AG, indicating that virus replication is required. Upregulation of WR and AG genes occurs during the critical period of CMV-accelerated TVS. Targeting these genes may prevent this process and improve allograft survival.

A fragile site in the human U2 small nuclear RNA gene cluster is revealed by adenovirus type 12 infection.

Using in situ hybridization, we found that the U2 small nuclear RNA gene cluster mapped very close to and was frequently disrupted by the gaps and breaks induced specifically in the human 17q21-q22 region by highly oncogenic adenovirus type 12 (Ad12). Restriction mapping revealed no structural alterations in the U2 gene locus as a result of Ad12 infection. Likewise, no Ad12-induced alterations in U2 RNA levels were detected. We estimate that the maximum size of the region specifically disrupted by this virus was less than 350 to 700 kilobases. A comparison of these data with similar data regarding biochemically induced fragile sites was made.

Restoration of telomeres in human papillomavirus-immortalized human anogenital epithelial cells.

Loss of telomeres has been hypothesized to be important in cellular senescence and may play a role in carcinogenesis. In this study, we have measured telomere length in association with the immortalization and transformation of human cervical and foreskin epithelial cells by the human papillomavirus type 16 or 18 E6 and E7 open reading frames. By using a telomeric TTAGGG repeat probe, it was shown that the telomeres of precrisis normal and E6-, E7-, and E6/E7-expressing cells gradually shortened with passaging (30 to 100 bp per population doubling). Cells that expressed both E6 and E7 went through a crisis period and gave rise to immortalized lines. In contrast to precrisis cells, E6/E7-immortalized cells generally showed an increase in telomere length as they were passaged in culture, with some later passage lines having telomeres that were similar to or longer than the earliest-passage precrisis cells examined. No consistent association could be made between telomere length and tumorigenicity of cells in nude mice. However, of the three cell lines that grew in vivo, two had long telomeres, thus arguing against the hypothesis that cancer cells favor shortened telomeres. Our results indicate that arrest of telomere shortening may be important in human papillomavirus-associated immortalization and that restoration of telomere length may be advantageous to cells with regard to their ability to proliferate.

Alteration of the DCC tumor-suppressor gene in tumorigenic HPV-18 immortalized human keratinocytes transformed by nitrosomethylurea.

A human papillomavirus type 18 (HPV-18)-immortalized human keratinocyte cell line (1811) has been transformed to tumorigenicity in nude mice by treatment with the carcinogen nitrosomethylurea (NMU). The NMU transformants (1811-NMU-T) showed additional chromosome alterations as compared with parental 1811 cells, including 18q deletion in two of two 1811-NMU-T lines analysed. Restriction fragment length polymorphism (RFLP) analysis indicated that both 1811-NMU-T lines had lost one allele of the 18q deleted in colon cancer (DCC) tumor-suppressor gene. Reverse transcriptase polymerase chain reaction (RT-PCR) showed that DCC expression was absent or barely detectable in the 1811-NMU-T cells as compared with 1811 or normal keratinocytes, suggesting that the remaining DCC allele in the 1811-NMU-T cells was also altered. These studies indicate that reduction or loss of DCC expression may be an important step in NMU transformation of HPV-immortalized cells to tumorigenicity.

Isolation and characterization of adenovirus-associated VA RNAs of human adenovirus type 7.

Two genes for virus-associated VA RNAs in the human adenovirus type 7 (Ad7) genome are compared to Ad2, Ad4, Ad5, simian VA RNAs, and pol III transcripts of Epstein-Barr virus. The newly identified VA RNA-encoding genes of Ad7 contain two relatively conserved intragenic promoter (elements A and B), the double-stranded RNA-dependent protein kinase (PK) active site-binding domain and transcriptional terminators. The conserved features extend to the VA RNA genes of simian and avian origin.

Improvement in disequilibrium symptoms during dialysis with low glucose dialyzate.

This study compares the frequency of dialysis disequilibrium symptoms (DDS), in 17 stable non-diabetic chronic hemodialysis patients, during a period using low glucose (200 mg/100 ml) dialyzate to a similar period using a glucose free dialyzate. There was a significant decrease in the total number of symptoms as well as the frequency of headache and post-dialysis fatigue during the low glucose period as compared to the glucose free period. The decrease in nausea or vomiting, and cramps was not significant while frequency of hypotension was unchanged. Evaluation of serum sodium, potassium, BUN, glucose and osmolarity did not reveal significant differences during the two periods. Dialysis with a low glucose bath produces less DDS than glucose free dialyzate.

Degradation of aliphatic halogen-substituted pesticides by dehalogenase isolated from Pseudomonas alcaligenes. Identification and properties of the enzyme.

Some characteristics of a 2,2-dichloropropionate dehalogenase induced in a bacterial strain capable of degrading high concentrations of the herbicide dalapon were studied. Polyacrilamide gel electrophoresis of the crude cell free extracts identified only one type of dehalogenase. The single enzymatic protein showed activity against a variety of chlorinated aliphatic acids but differed in their activity levels. Thus activity in mumol substrate converted (mg protein)-1 min-1 was 2-monochloropropionate 0.65, 2,2-dichloropropionate 0.56, 2-monochloroacetate 1.70 and 2,2-dichloroacetate 1.00. In the crude extracts, the enzyme activity against 2,2-dichloropropionate was optimal at a broad pH range with a mid-point at pH 9.5 and apparent Km values were within the range 0.23-0.73 mM.

Isolation of bovine adenovirus type 4 from cattle in Oregon.

Four isolates of bovine adenovirus type 4 were recovered from Oregon cattle. One isolate was recovered from a 1-week-old calf with pneumoenteritis, and 1 isolate from an 8-month-old bull with fever and respiratory disease. Two isolates were recovered as latent viruses in testicular cell cultures. All 4 isolates of the virus were shown to have certain physical, chemical, biologic, and antigenic characteristics similar to previously described strains of bovine adenovirus type 4. Of 246 adult beef and dairy cattle in Oregon, 51% had serum-viral neutralizing antibodies to the type 4 virus at the 1:8 dilution level.