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.

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.

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.

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.

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.

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.

Reactivation of latent human cytomegalovirus in CD14(+) monocytes is differentiation dependent.

We have previously demonstrated reactivation of latent human cytomegalovirus (HCMV) in myeloid lineage cells obtained from healthy donors. Virus was obtained from allogenically stimulated monocyte-derived macrophages (Allo-MDM), but not from macrophages differentiated by mitogenic stimulation (ConA-MDM). In the present study, the cellular and cytokine components essential for HCMV replication and reactivation were examined in Allo-MDM. The importance of both CD4(+) and CD8(+) T cells in the generation of HCMV-permissive Allo-MDM was demonstrated by negative selection or blocking experiments using antibodies directed against both HLA class I and HLA class II molecules. Interestingly, contact of monocytes with CD4 or CD8 T cells was not essential for reactivation of HCMV, since virus was observed in macrophages derived from CD14(+) monocytes stimulated by supernatants produced by allogeneic stimulation of peripheral blood mononuclear cells. Examination of the cytokines produced in Allo-MDM and ConA-MDM cultures indicated a significant difference in the kinetics of production and quantity of these factors. Further examination of the cytokines essential for the generation of HCMV-permissive Allo-MDM identified gamma interferon (IFN-gamma) but not interleukin-1 or -2, tumor necrosis factor alpha, or granulocyte-macrophage colony-stimulating factor as critical components in the generation of these macrophages. In addition, although IFN-gamma was crucial for reactivation of latent HCMV, addition of IFN-gamma to unstimulated macrophage cultures was insufficient to reactivate virus. Thus, this study characterizes two distinct monocyte-derived cell types which can be distinguished by their ability to reactivate and support HCMV replication and identifies the critical importance of IFN-gamma in the reactivation of HCMV.

The use of sacred story in a psychiatry spirituality group.

Describes the philosophy and methodology for using sacred stories from several religious traditions with psychiatric patients. Notes how chaplains are integrated into a psychiatric unit's interdisciplinary team. Details how sacred stories are selected for use in a spirituality group, how patients are screened for participation, and how the group is facilitated. Demonstrates the benefit and value patients and staff derive from a spirituality group on a psychiatric unit.

Long-term infection and transformation of dermal microvascular endothelial cells by human herpesvirus 8.

Human herpesvirus 8 (HHV8) infects Kaposi's sarcoma (KS) spindle cells in situ, as well as the lesional endothelial cells considered to be spindle cell precursors. The HHV8 genome contains several oncogenes, suggesting that infection of endothelial and spindle cells could induce cellular transformation and tumorigenesis and promote the formation of KS lesions. To investigate the potential of HHV8 infection of endothelial cells to contribute to the development of KS, we have developed an in vitro model utilizing dermal microvascular endothelial cells that support significant HHV8 infection. In contrast to existing in vitro systems used to study HHV8 pathogenesis, the majority of dermal endothelial cells are infected with HHV8 and the viral genome is maintained indefinitely. Infection is predominantly latent, with a small percentage of cells supporting lytic replication, and latency is responsive to lytic induction stimuli. Infected endothelial cells develop a spindle shape resembling that of KS lesional cells and show characteristics of a transformed phenotype, including loss of contact inhibition and acquisition of anchorage-independent growth. These results describe a relevant model system in which to study virus-host interactions in vitro and demonstrate the ability of HHV8 to induce phenotypic changes in infected endothelial cells that resemble characteristics of KS spindle cells in vivo. Thus, our results are consistent with a direct role for HHV8 in the pathogenesis of KS.

Human cytomegalovirus infection of caco-2 cells occurs at the basolateral membrane and is differentiation state dependent.

Epithelial cells are known to be a major target for human cytomegalovirus (HCMV) infection; however, the analysis of virus-cell interactions has been difficult to approach due to the lack of in vitro models. In this study, we established a polarized epithelial cell model using a colon epithelial cell-derived cell line (Caco-2) that is susceptible to HCMV infection at early stages of cellular differentiation. Infection of polarized cells was restricted to the basolateral surface whereas virus was released apically, which was consistent with the apical and not basolateral surface localization of two essential viral glycoproteins, gB and gH. HCMV infection resulted in the development of a cytopathology characteristic of HCMV infection of colon epithelium in vivo, and infection did not spread from cell to cell. The inability of HCMV to infect Caco-2 cells at late stages of differentiation was due to a restriction at the level of viral entry and was consistent with the sequestration of a cellular receptor for HCMV. These observations provide the first evidence that restriction of HCMV replication in epithelial cells is due to a receptor-mediated phenomenon.

A guide to finding and evaluating best practices health care information on the Internet: the truth is out there?

BACKGROUND: The advent of virtually free Internet access has opened large vistas of health care information to those willing to invest a small amount of time and energy learning how to perform searches using browser software. Health care providers, organizations, and professional associations, among many others, publish "best practices" information for both administrative and clinical audiences, making these recommendations among the fastest-growing types of health care information appearing on the World Wide Web. The problem is how to find best practices among the wealth of resources on the Internet and then how to separate the proverbial wheat from the chaff. WHO IS SEEKING BEST PRACTICES ON THE INTERNET? Best practice describes a process or technique whose employment results in improved patient and/or organizational outcomes. Health care providers, managed care organizations, administrators, payers, and policy analysts are all interested in improving the quality of health care and are likely to be customers of best practices informational resources. HOW TO EVALUATE THE QUALITY OF BEST PRACTICES INFORMATION? Once the information is available on the Internet, the problem for the searcher shifts from one of quantity to quality. The best practices information seeker should stop and ask a number of questions about the quality of information, its sources, and the methods used to obtain it. CONCLUSION: The "truth" may be out there some-where in cyberspace, but locating best practices information and evaluating its quality require new skills and patience and time to practice and develop them to the point of efficiency.

The enhancer domain of the human cytomegalovirus major immediate-early promoter determines cell type-specific expression in transgenic mice.

The human cytomegalovirus (HCMV) major immediate-early promoter (MIEP) is one of the first promoters to activate upon infection. To examine HCMV MIEP tissue-specific expression, transgenic mice were established containing the lacZ gene regulated by the MIEP (nucleotides -670 to +54). In the transgenic mice, lacZ expression was demonstrated in 19 of 29 tissues tested by histochemical and immunochemical analyses. These tissues included brain, eye, spinal cord, esophagus, stomach, pancreas, kidney, bladder, testis, ovary, spleen, salivary gland, thymus, bone marrow, skin, cartilage, and cardiac, striated and smooth muscles. Although expression was observed in multiple organs, promoter activity was restricted to specific cell types. The cell types which demonstrated HCMV MIEP expression included retinal cells of the eye, ductile cells of the salivary gland, exocrine cells of the pancreas, mucosal cells of the stomach and intestine, neuronal cells of the brain, muscle fibers, thecal cells of the corpus luteum, and Leydig and sperm cells of the testis. These observations indicate that the HCMV MIEP is not a pan-specific promoter and that the majority of expressing tissues correlate with tissues naturally infected by the virus in the human host.

Developmental analysis of the cytomegalovirus enhancer in transgenic animals.

The major immediate-early promoter (MIEP) of human, cytomegalovirus (HCMV) constitutes a primary genetic switch for viral activation. In this study, regulation of the enhancer-containing segment (nucleotides -670 to +54) of the HCMV MIEP attached to the 1acZ reporter gene was examined in the developing embryos of transgenic mice to identify temporal and tissue-specific expression. We find that the transgene reporter is first detected as a dorsal stripe of expression in the neural folds of embryos at day 8.5 postcoitum (p.c.). A broad expression pattern is exhibited in embryos at day 9.5 p.c. This pattern becomes more restricted by day 10.5 p.c. as organogenesis progresses. By day 14.5 p.c., prominent expression is observed in a subpopulation of central nervous system cells and spinal ganglia, endothelial cells, muscle, skin, thyroid, parathyroid, kidney, lung, liver, and gut cells, and the pancreas and submandibular and pituitary glands. This distribution pattern is discussed in relation to human congenital HCMV infection. These results suggest that the transcriptional activity of the HCMV MIEP may determine in part, the ability of the virus to specifically target developing fetal tissues in utero.

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.

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.

Interaction of HPV-18 and nitrosomethylurea in the induction of squamous cell carcinoma.

A strong correlation exists between the presence of specific types of human papillomavirus (HPV) and the development of anogenital cancer, as well as significant epidemiologic evidence suggesting smokers are at increased risk of developing cervical, vulvar and/or anal carcinomas. Primary and human papillomavirus type 18 (HPV-8)-immortalized human keratinocytes were used to address the co-carcinogenic potential of HPV and nitrosomethylurea (NMU) in tumorigenesis. Only cells containing HPV-18 and treated with NMU and the tumor-promoting phorbol ester, TPA, were transformed to a malignant phenotype. An in vitro system is described which initiates studies involving the mechanisms of HPV and chemical carcinogen co-operation in the etiology of squamous cell carcinomas.

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.