High adherence to intermittent and continuous use of a contraceptive vaginal ring among women in a randomized controlled trial in Kigali, Rwanda

Background: The introduction of female-initiated drug-delivery methods, including vaginal rings, have proven to be a promising avenue to address sexually transmitted infections and unintended pregnancies, which disproportionally affects women and girls in sub-Saharan Africa. Efficient uptake of existing and new technologies such as vaginal rings requires in depth understanding of product adherence. This remains a major challenge as data on adherence to vaginal rings from African countries is limited. In this study, we explored adherence of contraceptive vaginal ring (NuvaRing®) use in Kigali, Rwanda using a mixed methods approach. Methods: We collected quantitative and qualitative data at multiple time points from women participating in a clinical trial exploring the safety and acceptability of either intermittent or continuous use of the NuvaRing®. Various adherence categories were used including monthly and cumulative adherence measurement. The quantitative data were analysed using R and the qualitative data were analysed using a deductive, content-analytical approach based on categories related to the quantitative adherence measures. All data were compared and triangulated. Results: Data from 120 enrolled participants showed that self-reported adherence was high at every study visit in both study groups. At first study visit 80% of the intermittent ring users and 79.7% of the continuous ring users reported perfect adherence (assessed as “the ring was never out”). Reporting of ring expulsions and removals were highest (28.3%) at the beginning of the trial. Self-reported perfect ring adherence increased during the study and reports of ring expulsions and removals declined as familiarity with this contraceptive method increased. The percentage of women with perfect cumulative adherence was non-significantly higher in the intermittent (61.7%) than in the continuous use group (54.3%). The low rate of discrepant adherence data after triangulation (6%) is in line with the perception of the participants as adherent throughout the study. Conclusions: Self-reported adherence in both study groups was high with removals and expulsions being within the expected product range. Comprehensive adherence data triangulation allowed for a deeper understanding of context-driven behaviour that shaped adherence patterns and challenges. Our data categorisation and triangulation approach has shown potential for implementation in future vaginal ring studies aiming to better understand and measure adherence

The yeast protein kinase Sch9 adjusts V-ATPase assembly/disassembly to control pH homeostasis and longevity in response to glucose availability

The evolutionary conserved TOR complex 1 controls growth in response to the quality and quantity of nutrients such as carbon and amino acids. The protein kinase Sch9 is the main TORC1 effector in yeast. However, only few of its direct targets are known. In this study, we performed a genome-wide screening looking for mutants which require Sch9 function for their survival and growth. In this way, we identified multiple components of the highly conserved vacuolar proton pump (V-ATPase) which mediates the luminal acidification of multiple biosynthetic and endocytic organelles. Besides a genetic interaction, we found Sch9 also physically interacts with the V- ATPase to regulate its assembly state in response to glucose availability and TORC1 activity. Moreover, the interaction with the V-ATPase has consequences for ageing as it allowed Sch9 to control vacuolar pH and thereby trigger either lifespan extension or lifespan shortening. Hence, our results provide insights into the signaling mechanism coupling glucose availability, TORC1 signaling, pH homeostasis and longevity. As both Sch9 and the V-ATPase are highly conserved and implicated in various pathologies, these results offer fertile ground for further research in higher eukaryotes

Evaluation of cataract formation in fish exposed to environmental radiation at Chernobyl and Fukushima

Recent studies apparently finding deleterious effects of radiation exposure on cataract formation in birds and voles living near Chernobyl represent a major challenge to current radiation protection regulations. This study conducted an integrated assessment of radiation exposure on cataractogenesis using the most advanced technologies available to assess the cataract status of lenses extracted from fish caught at both Chernobyl in Ukraine and Fukushima in Japan. It was hypothesised that these novel data would reveal positive correlations between radiation dose and early indicators of cataract formation.The structure, function and optical properties of lenses were analysed from atomic to millimetre length scales. We measured the short-range order of the lens crystallin proteins using Small Angle X-Ray Scattering (SAXS) at both the SPring-8 and DIAMOND synchrotrons, the profile of the graded refractive index generated by these proteins, the epithelial cell density and organisation and finally the focal length of each lens.The results showed no evidence of a difference between the focal length, the epithelial cell densities, the refractive indices, the interference functions and the short-range order of crystallin proteins (X-ray diffraction patterns) in lens from fish exposed to different radiation doses. It could be argued that animals in the natural environment which developed cataract would be more likely, for example, to suffer predation leading to survivor bias. But the cross-length scale study presented here, by evaluating small scale molecular and cellular changes in the lens (pre-cataract formation) significantly mitigates against this issue

High adherence to intermittent and continuous use of a contraceptive vaginal ring among women in a randomized controlled trial in Kigali, Rwanda

BACKGROUND: The introduction of female-initiated drug-delivery methods, including vaginal rings, have proven to be a promising avenue to address sexually transmitted infections and unintended pregnancies, which disproportionally affects women and girls in sub-Saharan Africa. Efficient uptake of existing and new technologies such as vaginal rings requires in depth understanding of product adherence. This remains a major challenge as data on adherence to vaginal rings from African countries is limited. In this study, we explored adherence of contraceptive vaginal ring (NuvaRing®) use in Kigali, Rwanda using a mixed methods approach. METHODS: We collected quantitative and qualitative data at multiple time points from women participating in a clinical trial exploring the safety and acceptability of either intermittent or continuous use of the NuvaRing®. Various adherence categories were used including monthly and cumulative adherence measurement. The quantitative data were analysed using R and the qualitative data were analysed using a deductive, content-analytical approach based on categories related to the quantitative adherence measures. All data were compared and triangulated. RESULTS: Data from 120 enrolled participants showed that self-reported adherence was high at every study visit in both study groups. At first study visit 80% of the intermittent ring users and 79.7% of the continuous ring users reported perfect adherence (assessed as "the ring was never out"). Reporting of ring expulsions and removals were highest (28.3%) at the beginning of the trial. Self-reported perfect ring adherence increased during the study and reports of ring expulsions and removals declined as familiarity with this contraceptive method increased. The percentage of women with perfect cumulative adherence was non-significantly higher in the intermittent (61.7%) than in the continuous use group (54.3%). The low rate of discrepant adherence data after triangulation (6%) is in line with the perception of the participants as adherent throughout the study. CONCLUSIONS: Self-reported adherence in both study groups was high with removals and expulsions being within the expected product range. Comprehensive adherence data triangulation allowed for a deeper understanding of context-driven behaviour that shaped adherence patterns and challenges. Our data categorisation and triangulation approach has shown potential for implementation in future vaginal ring studies aiming to better understand and measure adherence

High adherence to intermittent and continuous use of a contraceptive vaginal ring among women in a randomized controlled trial in Kigali, Rwanda

BackgroundThe introduction of female-initiated drug-delivery methods, including vaginal rings, have proven to be a promising avenue to address sexually transmitted infections and unintended pregnancies, which disproportionally affects women and girls in sub-Saharan Africa. Efficient uptake of existing and new technologies such as vaginal rings requires in depth understanding of product adherence. This remains a major challenge as data on adherence to vaginal rings from African countries is limited. In this study, we explored adherence of contraceptive vaginal ring (NuvaRing®) use in Kigali, Rwanda using a mixed methods approach.MethodsWe collected quantitative and qualitative data at multiple time points from women participating in a clinical trial exploring the safety and acceptability of either intermittent or continuous use of the NuvaRing®. Various adherence categories were used including monthly and cumulative adherence measurement. The quantitative data were analysed using R and the qualitative data were analysed using a deductive, content-analytical approach based on categories related to the quantitative adherence measures. All data were compared and triangulated.ResultsData from 120 enrolled participants showed that self-reported adherence was high at every study visit in both study groups. At first study visit 80% of the intermittent ring users and 79.7% of the continuous ring users reported perfect adherence (assessed as “the ring was never out”). Reporting of ring expulsions and removals were highest (28.3%) at the beginning of the trial. Self-reported perfect ring adherence increased during the study and reports of ring expulsions and removals declined as familiarity with this contraceptive method increased. The percentage of women with perfect cumulative adherence was non-significantly higher in the intermittent (61.7%) than in the continuous use group (54.3%). The low rate of discrepant adherence data after triangulation (6%) is in line with the perception of the participants as adherent throughout the study.ConclusionsSelf-reported adherence in both study groups was high with removals and expulsions being within the expected product range. Comprehensive adherence data triangulation allowed for a deeper understanding of context-driven behaviour that shaped adherence patterns and challenges. Our data categorisation and triangulation approach has shown potential for implementation in future vaginal ring studies aiming to better understand and measure adherence

Biological mechanisms underlying ionising radiation-induced cataracts

Epidemiological data correlate exposure to ionising radiation (IR) with cataract formation. In 2012, the International Commission on Radiological Protection reduced its recommended threshold for IR effects on the eye lens to 0.5 Gy and acknowledged that the biological mechanisms underlying IR-induced cataracts are largely unknown. To determine these processes, the influence of IR on the lens epithelium, cholesterol and membrane proteins was investigated. CD1, C57BL/6J and B6C3F1 mice were exposed to 0.5 - 2 Gy at 0.3 or 0.063 Gy/ min. Lens epithelium cell density was examined at 4 and/ or 12 months post-IR. Differential response to IR in these mice was observed in a strain-, dose-, dose rate-, sex-, Ptch1+/- and Ercc2+/- -dependent manner and the data indicated that low dose IR-induced cataractogenesis requires a relatively long latency period, which is consistent with epidemiological data from longitudinal studies. The plasma membranes of lens fibre cells are among the cholesterol richest membranes in the human body and cholesterol has a vital role in biophysical properties of these membranes. Analysis of IR exposed bovine eye lens membrane extracts (5 and 50 Gy) and eye lenses taken from whole body irradiated mice (0.1 and 2 Gy) showed that IR induced a significant increase in cholesterol oxides i.e. oxysterols. Unlike the isolated lens membranes, the observed enhancement of oxysterol levels in vivo was transient. Furthermore, adding α-tocopherol to isolated lens cortex membranes before exposure to IR prevented the build-up of oxysterols. The increase of oxysterols in mice eye lenses was shown to also be age-related, and was observed in the hippocampus as well. In addition, a dose-dependent increase in protein glycation was noted after IR exposure of lens membrane extracts. Collectively, these data underline that IR contributes to the cataractogenic load through compromising lens membrane integrity and lens epithelium homeostasis

Commentary: APP as a Mediator of the Synapse Pathology in Alzheimer's Disease

status: Published onlin

Cataractogenic load – a concept to study the contribution of ionizing radiation to accelerated aging in the eye lens

Ionizing radiation (IR) damages DNA and other macromolecules, including proteins and lipids. Most cell types can repair DNA damage and cycle continuously their macromolecules as a mechanism to remove defective proteins and lipids. In those cells that lack nuclei and other organelles, such as lens fiber cells and mammalian erythrocytes, IR-induced damage to macromolecules is retained because they cannot be easily replenished. Whilst the life span for an erythrocyte is several months, the life span of a human lens is decades. There is very limited turnover in lens macromolecules, therefore the aging process greatly impacts lens structure and function over its lifetime. The lens is a tissue where biomolecular longevity, lifelong retention of its components and continued growth are integral to its homeostasis. These characteristics make the lens an excellent model to study the contribution of retained macromolecular damage over time. Epidemiological data have revealed a significant association between exposure to IR, the loss of lens optical function and the formation of cataracts (cataractogenesis) later in life. Lifestyle, genetic and environmental factors all contribute to cataractogenesis due to their effect on the aging process. Cataract is an iconic age-related disease in humans. IR is a recognised cause of cataract and the occupational lens dose limit is reduced from 150 to 20 mGy / year averaged over 5 years (ICRP Publication 118). Understanding the effects of low dose IR on the lens and its role in cataractogenesis is therefore very important. So we redefine “cataractogenic load” as a term to account for the combined lifestyle, genetic and environmental processes that increase biomolecular damage to lens macromolecules. These processes weaken metabolic defenses, increase post-translational protein modifications, and alter the lipid structure and content of the lens. IR exposure is a significant insult to the lens because of free radical generation and the ensuing oxidative stress. We support the concept that damage caused by IR compounds the aging process by increasing the cataractogenic load, hereby accelerating lens aging and its loss of function

Animal source food social and behavior change communication intervention among Girinka livestock transfer beneficiaries in Rwanda: A cluster randomized evaluation

Animal source foods (ASFs), including cow’s milk, contain essential nutrients and contribute to a healthy diet, but frequency of intake is low among children in low- and middle-income countries. We hypothesized that an ASF social and behavior change communication (SBCC) intervention implemented by community health workers (CHWs) would increase child milk consumption and dietary diversity in households that received a cow from the Government of Rwanda’s Girinka livestock transfer program. We tested the 9-month SBCC intervention among children aged 12–29 months at baseline in administrative cells randomly assigned to the intervention or control. Most mothers in the intervention group were exposed to CHWs’ home visits (90.7%) or community-level activities (82.8%). At endline, more mothers in the intervention group compared with the control group knew that cow’s milk was an ASF (90.1% vs. 81.7%, P=.03) and could be introduced to children at 12 months (41.7% vs. 18.7%, P<.001). More mothers in the intervention group compared with the control group knew they should feed their children ASFs (76.2% vs. 62.1%, P=.01) and give them 1 cup of cow’s milk per day (20.6% vs. 7.8%, P<.001). Children’s consumption of fresh cow’s milk 2 or more times per week increased in the intervention group, although not significantly (8.0 percentage points, P=.17); minimum dietary diversity was unchanged. Children in the intervention group had increased odds of consuming cow’s milk 2 or more times per week if their mothers recalled hearing that children should drink 1 cup of cow’s milk per day during a CHW’s home visit [odds ratio (OR) 2.1, 95% confidence interval (CI) (1.1, 3.9)] or a community activity [OR 2.0, 95% CI (1.2, 3.5)]. Approximately half of the children had no milk during the past week because their households produced too little or sold what was produced. In poor households receiving a livestock transfer, strategies to further tailor SBCC and increase cow’s milk production may be needed to achieve larger increases in children’s frequency of milk consumption