Promoting Teen Contraceptive Use by Intervention with Their Mothers

Introduction: The purpose of this pilot study was to test a community outreach model designed to help mothers in a rural, medically underserved area navigate their teen daughters to health department services for long-acting reversible contraception (LARC) or alternative contraception. Methods: The pilot study used a single-group, post-test only design. Mothers of teen daughters (N=142) received a 1-hour, one-to-one intervention session (in outreach settings) from Community Liaisons. Mothers received training on how to communicate with their daughters about LARC and other contraceptive methods. Data were collected from June through October 2014, and analyzed in September 2015. Results: The authors re-contacted 104 of 142 mothers enrolled in the study, achieving a 73.2% retention rate. Of these, 12.5% had daughters receiving LARC. An additional 11.0% had daughters with health department–verified initiation of birth control pills. Only one correlate—whether a mother believed her daughter was having sex—was associated with receiving either LARC or birth control pills. Among those indicating they knew their daughters were having sex, 31.7% of the daughters received LARC/birth control pills. By contrast, among mothers not indicating they knew their daughters were having sex, only 2.9% had daughters receiving LARC or birth control pills. Conclusions: Findings suggest that an outreach-based program delivered directly to mothers of teen daughters may be a highly effective method for enhancing service utilization of LARC and the initiation of birth control pill use in a rural, medically underserved area

Evaluation of textile substrates for dispensing synthetic attractants for malaria mosquitoes

Background: The full-scale impact of odour-baited technology on the surveillance, sampling and control of vectors of infectious diseases is partly limited by the lack of methods for the efficient and sustainable dispensing of attractants. In this study we investigated whether locally-available and commonly used textiles are efficient substrates for the release of synthetic odorant blends attracting malaria mosquitoes. Methods: The relative efficacy of (a) polyester, (b) cotton, (c) cellulose + polyacrylate, and (d) nylon textiles as substrates for dispensing a synthetic odour blend (Ifakara blend 1(IB1)) that attracts malaria mosquitoes was evaluated in western Kenya. The study was conducted through completely randomized Latin square experimental designs under semi-field and field conditions. Results: Traps charged with IB1-impregnated polyester, cotton and cellulose + polyacrylate materials caught significantly more female Anopheles gambiae sensu stricto (semi-field conditions) and An. gambiae sensu lato (field conditions) mosquitoes than IB1-treated nylon (P = 0.001). The IB1-impregnated cellulose + polyacrylate material was the most attractive to female An. funestus mosquitoes compared to all other dispensing textile substrates (P < 0.001). The responses of female An. funestus mosquitoes to IB1-treated cotton and polyester were equal (P = 0.45). Significantly more female Culex mosquitoes were attracted to IB1-treated cotton than to the other treatments (P < 0.001). Whereas IB1-impregnated cotton and cellulose + polyacrylate material attracted equal numbers of female Mansonia mosquitoes (P = 0.44), the catches due to these two substrates were significantly higher than those associated with the other substrates (P < 0.001). Conclusion: The number and species of mosquitoes attracted to a synthetic odour blend is influenced by the type of odour-dispensing material used. Thus, surveillance and intervention programmes for malaria and other mosquito vectors using attractive odour baits should select an odour-release material that optimizes the odour blend

Self-Collected Vaginal Swabs for HPV Screening: An Exploratory Study of Rural Black Mississippi Women

Objectives. To determine the post-procedure acceptability of self-collecting a vaginal swab for HPV testing among a highly impoverished and geographically isolated population of medically underserved Black women residing in the Mississippi Delta. Further, to test correlates of reporting that self-collection is preferred over Pap testing. Finally, to determine the prevalence of any of 13 high-risk HPV types among this population and the correlates of testing positive. Methods. Eighty-eight women were recruited from two churches located in different towns of the Mississippi Delta. After completing a survey, women were provided instructions for self-collecting a cervico-vaginal swab and completing a post-collection survey. Specimens were tested for 13 oncogenic HPV types. Due to the exploratory nature of the study, significance was defined by a 0.15 alpha-level. Results. Comfort levels with self-collection were high: 78.4% indicated a preference for self-collecting a specimen compared to Pap testing. Overall, 24 women (28.7%) tested positive for one or more of the 13 HPV types. Significant associations with testing positive were found for women having sex with females (P = 0.09), those never having an abnormal Pap (P = 0.06), younger women (P = 0.10), those with greater fatalism scores (P = 0.006), and those having less trust in doctors (P = 0.001). Conclusions. Black rural women from the deep-south are generally comfortable self-collecting cervico-vaginal swabs for HPV testing. Given that nearly 30% tested positive for oncogenic HPV, and that fatalism as well a lack of trust in doctors predicted prevalence, a reasonable screening alternative to Pap testing may be community-based testing for HPV using self-collected vaginal swabs

Healthcare professionals' preferences for surgery or primary endocrine therapy to treat older women with operable breast cancer

Introduction : Primary endocrine therapy (PET) is an alternative treatment to surgery for oestrogen receptor (ER) positive operable breast cancer in older women. However, there is variable use of PET in the UK, with up to 40% of patients aged over 70 receiving PET instead of surgery in some regions. Treatment options offered to patients rely heavily on healthcare professional (HCP) assessment and opinion on which treatments are appropriate. Materials and methods : This was a mixed methods study combining semi-structured interviews with HCPs working in high and low PET regions in the UK, followed by a postal questionnaire survey distributed via the Association of Breast Surgery (ABS). Results : Thirty-four HCPs (20 breast surgeons; 13 nurse specialists; 1 geriatrician) were interviewed from 14 sites across the UK and 252/641 questionnaires returned (39%). There was an overriding view that PET is not suitable for patients under the age of 80 unless there are significant comorbidities. Opinion was split regarding the best way to treat patients with dementia. Patient preference was generally stated to be the most important factor when considering treatment, however only around a quarter 65/244 (26.6%) felt that all patients over the age of 70 should be offered PET as an alternative treatment option. Conclusions : Opinions differ on the best way to treat women over 70 with operable breast cancer, especially if they have co-existing dementia, as well as whether they should be offered PET as a treatment option. This may be a significant cause of treatment variation in the UK. Keywords : Breast cancer; Primary endocrine therapy; Surgery; Elderly; Older; Mixed methods.</p

SNX27–Retromer directly binds ESCPE-1 to transfer cargo proteins during endosomal recycling

Coat complexes coordinate cargo recognition through cargo adaptors with biogenesis of transport carriers during integral membrane protein trafficking. Here, we combine biochemical, structural, and cellular analyses to establish the mechanistic basis through which SNX27-Retromer, a major endosomal cargo adaptor, couples to the membrane remodeling endosomal SNX-BAR sorting complex for promoting exit 1 (ESCPE-1). In showing that the SNX27 FERM (4.1/ezrin/radixin/moesin) domain directly binds acidic-Asp-Leu-Phe (aDLF) motifs in the SNX1/SNX2 subunits of ESCPE-1, we propose a handover model where SNX27-Retromer captured cargo proteins are transferred into ESCPE-1 transport carriers to promote endosome-to-plasma membrane recycling. By revealing that assembly of the SNX27:Retromer:ESCPE-1 coat evolved in a stepwise manner during early metazoan evolution, likely reflecting the increasing complexity of endosome-to-plasma membrane recycling from the ancestral opisthokont to modern animals, we provide further evidence of the functional diversification of yeast pentameric Retromer in the recycling of hundreds of integral membrane proteins in metazoans

Structure-guided fragment-based drug discovery at the synchrotron: screening binding sites and correlations with hotspot mapping.

Structure-guided drug discovery emerged in the 1970s and 1980s, stimulated by the three-dimensional structures of protein targets that became available, mainly through X-ray crystal structure analysis, assisted by the development of synchrotron radiation sources. Structures of known drugs or inhibitors were used to guide the development of leads. The growth of high-throughput screening during the late 1980s and the early 1990s in the pharmaceutical industry of chemical libraries of hundreds of thousands of compounds of molecular weight of approximately 500 Da was impressive but still explored only a tiny fraction of the chemical space of the predicted 1040 drug-like compounds. The use of fragments with molecular weights less than 300 Da in drug discovery not only decreased the chemical space needing exploration but also increased promiscuity in binding targets. Here we discuss advances in X-ray fragment screening and the challenge of identifying sites where fragments not only bind but can be chemically elaborated while retaining their positions and binding modes. We first describe the analysis of fragment binding using conventional X-ray difference Fourier techniques, with Mycobacterium abscessus SAICAR synthetase (PurC) as an example. We observe that all fragments occupy positions predicted by computational hotspot mapping. We compare this with fragment screening at Diamond Synchrotron Light Source XChem facility using PanDDA software, which identifies many more fragment hits, only some of which bind to the predicted hotspots. Many low occupancy sites identified may not support elaboration to give adequate ligand affinity, although they will likely be useful in drug discovery as 'warm spots' for guiding elaboration of fragments bound at hotspots. We discuss implications of these observations for fragment screening at the synchrotron sources. This article is part of the theme issue 'Fifty years of synchrotron science: achievements and opportunities'.The Botnar Foundation (grant number: 6063), the Cystic Fibrosis Trust (Strategic Research Centre Awards 002, 010 & 201) and the Bill and Melinda Gates Foundation, Shorten-TB Award

Concussion-associated gene variants and history of concussion in elite male rugby athletes

Occurrence of and outcomes following a concussion are probably affected by the interaction of multiple genes in a polygenic manner [1,2]. This study investigated whether suspected concussion-associated polygenic profiles of elite rugby athletes with a history of previous concussion (RAC) differed from rugby athletes with no history of previous concussion (RANC). We hypothesised that concussion-associated risk genotypes would be underrepresented in RANC compared to RAC. Participants were from the RugbyGene project, comprising elite male rugby athletes (RA) (185 white males; mean (standard deviation) height 1.86 (0.07) m, mass 102 (12.6) kg, age 26.4 (5.1) yr) competing at an elite level in rugby union (n = 165) and league (n = 20) in the UK, Ireland, Italy and South Africa. Concussion history was collected using a self-reported concussion history questionnaire. PCR of genomic DNA was used to determine genotypes using TaqMan probes, and total genotype scores (TGS) were calculated, then groups were compared using χ2 and odds ratio (OR) statistics. In addition, multifactor dimensionality reduction (MDR) was used to identify genetic interactions. Seventy-eight percent of RA reported a history of sustaining at least one concussion and 54% of RA reported sustaining multiple (≥2) concussions from rugby. For BDNF-AS rs6265, the GG genotype was more common in RAC compared to RANC (69.7% vs 61.0%, P = 0.006, OR = 9.90, 95% CI = 01.81-54.06) (Fig. 1). The GG genotype of BDNF-AS rs6265 was more common in RAC compared to RANC (70.7% vs. 61.0%, P = 0.041, OR 4.44, 95% CI = 1.04-120.97) (Fig. 1). However, TGS did not differ between RANC and RAC (Fig. 2A) recovery duration and family history of neurological conditions (P > 0.05). Receiver operating characteristic curve (ROC) and area under the curve (AUC) analysis confirmed the TGS algorithm could not identify concussion history (AUC = 0.436; 95% CI = 0.338-0.534; P = 0.218; Fig. 2B). MDR could not identify a model to predict concussion history, recovery duration and family history of neurological conditions with a sufficiently powerful cross-validation statistic (P ≤ 0.05). These findings support the growing evidence that incidence and recovery from concussion could be influenced by an athlete’s genetic predisposition. Such knowledge could be used in the future and when additional relevant variants have been identified, to inform individualised management strategies for athletes in possession of risk genotypes.Peer reviewe