Self-sampling as the principal modality for population based cervical screening: Five-year follow-up of the PaVDaG study.

Self-sampling provides a powerful means to engage women in cervical screening. In the original Papillomavirus Dumfries and Galloway study (PaVDaG), we demonstrated cross-sectional similarity of high-risk human papillomavirus (Hr-HPV) testing on self-taken vaginal vs clinician-taken samples for the detection of cervical intraepithelial neoplasia 2 or worse (CIN2+). Few data exist on the longitudinal performance of self-sampling; we present longitudinal outcomes of PaVDaG. Routinely screened women provided a self-taken and a clinician-collected sample. Ninety-one percent of 5136 women from the original cohort completed a further screening round. Sensitivity, specificity, positive predictive value and complement of the negative predictive value of the Hr-HPV test on self-samples for detection of CIN2+ and CIN3+ up-to 5 years after testing were determined. Additionally, clinical accuracy of Hr-HPV testing on vaginal and clinician-collected samples was assessed. A total of 183 CIN2+ and 102 CIN3+ lesions were diagnosed during follow-up. Risk of CIN2+ and CIN3+ following an Hr-HPV negative self-sample was 0.6% and 0.2%, respectively, for up to 5 years after testing. The relative sensitivity for CIN3+ and specificity for ≤CIN1 of Hr-HPV testing on self-taken specimens was slightly lower vs clinician-collected samples: 0.95 (95% CI: 0.90-0.99; PMcN = .0625) and 0.98 (95% CI: 0.95-1.00; PMcN = <.0000), respectively. The low risk of CIN2+ in women with Hr-HPV-self-sample(s) suggests, that the 3 to 5-year recall interval implemented in several cervical screening settings, based on clinician-taken samples, may be safe for self-samples. Future assessment will show if "universal" 5-year screening is appropriate for programs based on self-sampling.

Silk-silica composites from genetically engineered chimeric proteins: materials properties correlate with silica condensation rate and colloidal stability of the proteins in aqueous solution.

The aim of the study was to determine the extent and mechanism of influence on silica condensation that is presented by a range of known silicifying recombinant chimeras (R5: SSKKSGSYSGSKGSKRRIL; A1: SGSKGSKRRIL; and Si4-1: MSPHPHPRHHHT and repeats thereof) attached at the N-terminus end of a 15-mer repeat of the 32 amino acid consensus sequence of the major ampullate dragline Spindroin 1 (Masp1) Nephila clavipes spider silk sequence ([SGRGGLGGQG AGAAAAAGGA GQGGYGGLGSQG](15)X). The influence of the silk/chimera ratio was explored through the adjustment of the type and number of silicifying domains (denoted X above), and the results were compared with their non-chimeric counterparts and the silk from Bombyx mori. The effect of pH (3-9) on reactivity was also explored. Optimum conditions for rate and control of silica deposition were determined, and the solution properties of the silks were explored to determine their mode(s) of action. For the silica-silk-chimera materials formed there is a relationship between the solution properties of the chimeric proteins (ability to carry charge), the pH of reaction, and the solid state materials that are generated. The region of colloidal instability correlates with the pH range observed for morphological control and coincides with the pH range for the highest silica condensation rates. With this information it should be possible to predict how chimeric or chemically modified proteins will affect structure and morphology of materials produced under controlled conditions and extend the range of composite materials for a wide spectrum of uses in the biomedical and technology fields.

Bioinspired silicification of silica-binding peptide-silk protein chimeras: comparison of chemically and genetically produced proteins.

Novel protein chimeras constituted of "silk" and a silica-binding peptide (KSLSRHDHIHHH) were synthesized by genetic or chemical approaches and their influence on silica-silk based chimera composite formation evaluated. Genetic chimeras were constructed from 6 or 15 repeats of the 32 amino acid consensus sequence of Nephila clavipes spider silk ([SGRGGLGGQG AGAAAAAGGA GQGGYGGLGSQG](n)) to which one silica binding peptide was fused at the N terminus. For the chemical chimera, 28 equiv of the silica binding peptide were chemically coupled to natural Bombyx mori silk after modification of tyrosine groups by diazonium coupling and EDC/NHS activation of all acid groups. After silica formation under mild, biomaterial-compatible conditions, the effect of peptide addition on the properties of the silk and chimeric silk-silica composite materials was explored. The composite biomaterial properties could be related to the extent of silica condensation and to the higher number of silica binding sites in the chemical chimera as compared with the genetically derived variants. In all cases, the structure of the protein/chimera in solution dictated the type of composite structure that formed with the silica deposition process having little effect on the secondary structural composition of the silk-based materials. Similarly to our study of genetic silk based chimeras containing the R5 peptide (SSKKSGSYSGSKGSKRRIL), the role of the chimeras (genetic and chemical) used in the present study resided more in aggregation and scaffolding than in the catalysis of condensation. The variables of peptide identity, silk construct (number of consensus repeats or silk source), and approach to synthesis (genetic or chemical) can be used to "tune" the properties of the composite materials formed and is a general approach that can be used to prepare a range of materials for biomedical and sensor-based applications.

Clinical Performance of Triage Strategies for Hr-HPV-Positive Women; A Longitudinal Evaluation of Cytology, p16/K-67 Dual Stain Cytology, and HPV16/18 Genotyping.

BACKGROUND: We evaluated the longitudinal performance of three options: HPV16/18 genotyping (HPV16/18), cytology (LBC), and p16/Ki-67 dual stain cytology (DS) for the triage of high-risk Human Papillomavirus-positive (Hr-HPV+) women within the cervical screening program in Scotland. METHODS: Data were derived from a cohort of Hr-HPV+ women (n = 385) who participated in PaVDaG (Papillomavirus Dumfries and Galloway) study. Performance of triage strategies for detecting high-grade disease was assessed at 3 (in women <50 years) or 5 years (in women >50 years). Sensitivity, specificity, PPV, and cNPV of each triage test were calculated for CIN2+ and CIN3+ when used singly or sequentially. RESULTS: The sensitivity of LBC (≥ borderline), DS, and HPV 16/18 genotyping for the detection of CIN2+ was 62.7% (50.7-73.3), 77.7% (63.1-83.7), and 62.7% (50.7-73.3) with corresponding cNPVs of 10.9%, 8.4%, and 11.9%. The option with the highest sensitivity and lowest cNPV was HPV 16/18 genotyping followed by LBC of Hr-HPV other+ and then DS of the LBC negatives. This yielded sensitivity of 94.7% (86.2-98.3) and cNPV 2.7% for CIN2+. Triage performance was similar if women had tested Hr-HPV+ positive by vaginal self-sampling. CONCLUSIONS: Two-step triage with HPV 16/18 genotyping before LBC (or DS) for Hr-HPV other+ women was associated with a lower risk of significant disease at follow-up compared with single triage approaches. IMPACT: This study provides longitudinal performance data on triage strategies in Hr-HPV+ women and will be informative for the evolution of cervical screening programs that increasingly rely on molecular technologies.

Vision for menopause care in the UK.

Menopause is a major life event affecting all women in a variety of ways, both short and long term. All women should have access to accurate information, available in all forms and through all recognised sources. All healthcare professionals should have a basic understanding of the menopause and know where to signpost women for advice, support and treatment whenever appropriate. Every primary care team should have at least one nominated healthcare professional with a special interest and knowledge in menopause. All healthcare professionals with a special interest in menopause should have access to British Menopause Society Menopause Specialists for advice, support, onward referral and leadership of multidisciplinary education. With the introduction of the comprehensive British Menopause Society Principles and Practice of Menopause Care programme, the society is recognised throughout the UK as the leading provider of certificated menopause and post reproductive health education and training for healthcare professionals. Restrictions imposed by the coronavirus pandemic have been a springboard for the British Menopause Society to bring innovations to the services provided for our membership and for healthcare professionals throughout the UK.

Silica in plants: biological, biochemical and chemical studies.

BACKGROUND: The incorporation of silica within the plant cell wall has been well documented by botanists and materials scientists; however, the means by which plants are able to transport silicon and control its polymerization, together with the roles of silica in situ, are not fully understood. RECENT PROGRESS: Recent studies into the mechanisms by which silicification proceeds have identified the following: an energy-dependent Si transporter; Si as a biologically active element triggering natural defence mechanisms; and the means by which abiotic toxicities are alleviated by silica. A full understanding of silica formation in vivo still requires an elucidation of the role played by the environment in which silica formation occurs. Results from in-vitro studies of the effects of cell-wall components associated with polymerized silica on mineral formation illustrate the interactions occurring between the biomolecules and silica, and the effects their presence has on the mineralized structures so formed. SCOPE: This Botanical Briefing describes the uptake, storage and function of Si, and discusses the role biomolecules play when incorporated into model systems of silica polymerization as well as future directions for research in this field.

Facial burning in women with leprosy, physiological or pathological?

INTRODUCTION: Eight peri-menopausal women, five with borderline lepromatous leprosy and three with borderline tuberculoid leprosy, self-referred complaining of 'burning of the face. Four were seen in 1993, three having been treated as 'menopausal'without betterment and four were seen in 1997. METHODS: Eight peri-menopausal women who self-referred because of facial burning', and seven women who self-referred for other problems had a careful review of clinical records and were assessed fully for leprosy including graded sensory skin testing of the face, and standard nerve function tests. RESULTS: On examination three in each group of four complaining of facial burning were found to have major loss of facial sensation and one had generalised neuritis without significant facial involvement. Treatment with antileprotics and steroids resulted in recovery of facial sensation, although one later became blind. Of the seven who self-referred without facial burning, five had no facial sensory loss and two had slight loss of facial sensation.

Defining Optimal Triage Strategies for hrHPV Screen-Positive Women-An Evaluation of HPV 16/18 Genotyping, Cytology, and p16/Ki-67 Cytoimmunochemistry.

Background: Several options for the triage of high-risk HPV screen-positive (hrHPV+) women were assessed.Methods: This study incorporated CIN2+ cases and controls, all of whom tested hrHPV+ and whose results of liquid-based cytology (LBC), HPV16/18 genotyping, and p16/Ki67 cytoimmunochemistry were available. Sensitivity and specificity for the CIN2+ of these triage tests were evaluated.Results: Absolute sensitivities of HPV 16/18 typing, LBC, and p16/Ki-67 cytoimmunochemistry for CIN2+ detection were 61.7%, 68.3%, and 85.0% for women with hrHPV+ clinician-taken samples. Respective specificities were 70.5%, 89.1%, and 76.7%. The absolute accuracy of the triage tests was similar for women with a hrHPV+ self-sample. P16/Ki-67 cyto-immunochemistry was significantly more sensitive than LBC although significantly less specific.Conclusions: All three single-test triage options, if positive, exceed the threshold of 20% risk at which colposcopy would be indicated. However, none of them conferred a post-test probability of CIN2+ <2%; which would permit routine recall. P16/Ki-67 cytoimmunochemistry on HPV16/18 negative women had a post-test probability of CIN2+ of 1.7% and 0.6% if also LBC negative.Impact: This is one of the few studies to directly compare the performance of triage strategies of hrHPV+ women, in isolation and combinations. It is the only study assessing triage strategies in women who test hrHPV+ in self-taken vaginal samples. A combined triage option that incorporated HPV 16/18 typing prior to p16/ki-67 cytoimmunochemistry in HPV 16/18-negative women yielded a post-test probability of CIN2+ of >20%, whereas women who tested negative had a probability of CIN2+ of <2%. Cancer Epidemiol Biomarkers Prev; 26(11); 1629-35. ©2017 AACR.

Resolution of complex monosaccharide mixtures from plant cell wall isolates by high pH anion exchange chromatography.

The use of high pH anion exchange chromatography combined with pulsed amperometric detection has been established as an effective and sensitive method for the separation, detection and quantification of monosaccharides from a wide range of sources. However, careful examination of the separation conditions required is necessary to ensure that a complete monosaccharide profile can be determined from structures such as the plant cell wall which is a complex network of both neutral and charged polysaccharides. This study has investigated the optimal conditions required for the analysis of such a challenging mixture, including both the stationary and mobile phase minimising co-elution and reducing method complexity. The preferred methods have been used to successfully identify and quantify the monosaccharide components of a selected extract from the plant cell wall of the primitive higher plant Equisetum arvense.

Reducing inappropriate testing in the diagnosis of the menopause and peri-menopause.

The menopause should be diagnosed based on age, menstrual history and clinical symptoms, and as such, follicle stimulating hormone testing may be considered inappropriate when diagnosing the menopause or peri-menopause in women aged 45 and over. As part of a demand optimisation programme, the number of follicle stimulating hormone tests requested to diagnose the menopause in this age group was quantified and educational interventions were implemented to reduce inappropriate testing. The number of follicle stimulating hormone tests requested to diagnose the menopause in women aged 45 and over was successfully and sustainably reduced.

Clinical validation of hrHPV testing on vaginal and urine self-samples in primary cervical screening (cross-sectional results from the Papillomavirus Dumfries and Galloway-PaVDaG study).

OBJECTIVES: Papillomavirus Dumfries and Galloway (PaVDaG) assessed the performance of a high-risk human papillomavirus (hrHPV) PCR-based assay to detect high-grade cervical intraepithelial neoplasia (CIN2+) in self-collected vaginal and urine samples. SETTING: Women attending routine cervical screening in primary care. PARTICIPANTS: 5318 women aged 20-60 years provided self-collected random urine and vaginal samples for hrHPV testing and a clinician-collected liquid-based cytology (LBC) sample for cytology and hrHPV testing. INTERVENTIONS: HrHPV testing. All samples were tested for hrHPV using the PCR-based cobas 4800 assay. Colposcopy was offered to women with high-grade or repeated borderline/low-grade cytological abnormalities; also to those who were LBC negative but hrHPV 16/18 positive. PRIMARY AND SECONDARY OUTCOME MEASURES: The self-tests' absolute sensitivity and specificity for CIN2+ were assessed on all biospecimens; also, their relative sensitivity and specificity compared with clinician-taken samples. Interlaboratory and intralaboratory performance of the hrHPV assay in self-collected samples was also established. RESULTS: HrHPV prevalence was 14.7%, 16.6% and 11.6% in cervical, vaginal and urine samples, respectively. Sensitivity for detecting CIN2+ was 97.7% (95% to 100%), 94.6% (90.7% to 98.5%) and 63.1% (54.6% to 71.7%) for cervical, vaginal and urine hrHPV detection, respectively. The corresponding specificities were 87.3% (86.4% to 88.2%), 85.4% (84.4% to 86.3%) and 89.8% (89.0% to 90.7%). There was a 38% (24% to 57%) higher HPV detection rate in vaginal self-samples from women over 50 years compared with those ≤29 years. Relative sensitivity and specificity of hrHPV positivity for the detection of CIN2+ in vaginal versus cervical samples were 0.97 (0.94 to 1.00) and 0.98 (0.97 to 0.99); urine versus cervical comparisons were 0.53 (0.42 to 0.67) and 1.03 (1.02 to 1.04). The intralaboratory and interlaboratory agreement for hrHPV positivity in self-samples was high (κ values 0.98 (0.96 to 0.99) and 0.94 (0.92 to 0.97) for vaginal samples and 0.95 (0.93 to 0.98) and 0.90 (0.87 to 0.94) for urine samples). CONCLUSIONS: The sensitivity of self-collected vaginal samples for the detection of CIN2+ was similar to that of cervical samples and justifies consideration of this sample for primary screening.

Behaviours and attitudes influencing treatment decisions for menopausal symptoms in five European countries.

OBJECTIVE: To assess women's behaviours and attitudes regarding the treatment of menopausal symptoms in five European countries. STUDY DESIGN: Women aged ≥45 years in France, Germany, Italy, Spain, and the United Kingdom participated in an internet survey. Completers were those who reported menopausal symptoms and had treated their symptoms. Women were equally stratified by age (45-54 years, 55-64 years, ≥65 years). MAIN OUTCOME MEASURES: Behaviours, attitudes, and experiences regarding treatment of menopausal symptoms. RESULTS: Of 3890 peri- to postmenopausal women screened, 67% experienced symptoms and 54% sought either medical input or some treatment concerning their symptoms. Hot flushes, the most common symptom, decreased with age but remained prevalent after age 64. Roughly 75% of women who sought relief consulted a physician, mostly a gynaecologist or a general practitioner (GP) as in the United Kingdom. The decision to seek treatment was influenced by age, number, and severity of symptoms. Approximately 79% visiting a physician received prescription therapy. Of the women who received non-hormone therapy (HT) treatment instead of HT: patients refused HT (20-44%), physicians did not discuss HT (32-46%), or advised against HT (24-43%). Women in the United Kingdom were most familiar with and favorable to HT. Interest in a new HT (34-50%) was higher than use (19-28%). CONCLUSIONS: Menopausal symptoms are common, persistent, and bothersome, but many fail to seek treatment. Sources and types of treatment vary among age groups and countries. Education regarding women's attitudes toward treatment should be provided to those physicians who treat menopausal symptoms in each country.

The Internet and the menopause consultation: menopause management in the third millennium.

The Internet was born in 1969; it was originally developed so that computers could share information on research and development in the scientific and military fields. The original Internet consisted of four university computers networked in the United States. Email became available two years later. The infant Internet initially required complex computing knowledge to be used. However, this was all to change with the development of the World Wide Web in the early 1990s, which made the Internet much more widely accessible. The Internet has since grown at a phenomenal rate and has evolved into a global communications tool. It is by nature anarchic, in that it is an unrestricted broadcast medium. Although this lack of censorship is a strength, it is also a weakness. The quality of information available on the Web is variable and discernment is required. With the growth of e-health, medicine and its allied specialties are faced with the challenges of providing their services in a novel way while maintaining the first principle of medicine, primum non nocere (first, do no harm). This provision of e-health care is in its infancy and this review explores issues arising from the use of the Internet as a medium for organizing menopausal health care in the third millennium.