Association of dietary flavan-3-ol intakes with plasma phenyl-γ-valerolactones: analysis from the TUDA cohort of healthy older adults.

BACKGROUND: Dietary polyphenols, including flavan-3-ols (F3O), are associated with better health outcomes. The relationship of plasma phenyl-γ-valerolactones (PVLs), the products of colonic bacterial metabolism of F3O, with dietary intakes is unclear. OBJECTIVES: To investigate whether plasma PVLs are associated with self-reported intakes of total F3O and procyanidins+(epi)catechins. DESIGN: We measured 9 PVLs by uHPLC-MS-MS in plasma from adults (>60y) in the Trinity-Ulster-Department of Agriculture (TUDA study (2008 to 2012; n=5186) and a follow-up subset (2014 to 2018) with corresponding dietary data (n=557). Dietary (poly)phenols collected by FFQ were analyzed using Phenol-Explorer. RESULTS: Mean (95% confidence interval [CI]) intakes were estimated as 2283 (2213, 2352) mg/d for total (poly)phenols, 674 (648, 701) for total F3O, and 152 (146, 158) for procyanidins+(epi)catechins. Two PVL metabolites were detected in plasma from the majority of participants, 5-(hydroxyphenyl)-γ-VL-sulfate (PVL1) and 5-(4'-hydroxyphenyl)-γ-VL-3'-glucuronide (PVL2). The 7 other PVLs were detectable only in 1-32% of samples. Self-reported intakes (mg/d) of F3O (r = 0.113, P = 0.017) and procyanidin+(epi)catechin (r = 0.122, P = 0.010) showed statistically significant correlations with the sum of PVL1 and PVL 2 (PVL1+2). With increasing intake quartiles (Q1-Q4), mean (95% CI) PVL1+2 increased; from 28.3 (20.8, 35.9) nmol/L in Q1 to 45.2 (37.2, 53.2) nmol/L in Q4; P = 0.025, for dietary F3O, and from 27.4 (19.1, 35.8) nmol/L in Q1 to 46.5 (38.2, 54.9) nmol/L in Q4; P = 0.020, for procyanidins+(epi)catechins. CONCLUSIONS: Of 9 PVL metabolites investigated, 2 were detected in most samples and were weakly associated with intakes of total F3O and procyanidins+(epi)catechins. Future controlled feeding studies are required to validate plasma PVLs as biomarkers of these dietary polyphenols.

Spatio-temporal monitoring of health facility-level malaria trends in Zambia and adaptive scaling for operational intervention.

Background: The spatial and temporal variability inherent in malaria transmission within countries implies that targeted interventions for malaria control in high-burden settings and subnational elimination are a practical necessity. Identifying the spatio-temporal incidence, risk, and trends at different administrative geographies within malaria-endemic countries and monitoring them in near real-time as change occurs is crucial for developing and introducing cost-effective, subnational control and elimination intervention strategies. Methods: This study developed intelligent data analytics incorporating Bayesian trend and spatio-temporal Integrated Laplace Approximation models to analyse high-burden over 32 million reported malaria cases from 1743 health facilities in Zambia between 2009 and 2015. Results: The results show that at least 5.4 million people live in catchment areas with increasing trends of malaria, covering over 47% of all health facilities, while 5.7 million people live in areas with a declining trend (95% CI), covering 27% of health facilities. A two-scale spatio-temporal trend comparison identified significant differences between health facilities and higher-level districts, and the pattern observed in the southeastern region of Zambia provides the first evidence of the impact of recently implemented localised interventions. Conclusions: The results support our recommendation for an adaptive scaling approach when implementing national malaria monitoring, control and elimination strategies and a particular need for stratified subnational approaches targeting high-burden regions with increasing disease trends. Strong clusters along borders with highly endemic countries in the north and south of Zambia underscore the need for coordinated cross-border malaria initiatives and strategies.

Effects of maternal folic acid supplementation during the second and third trimesters of pregnancy on neurocognitive development in the child: an 11-year follow-up from a randomised controlled trial.

BACKGROUND: Maternal folic acid (FA) supplementation before and in early pregnancy prevents neural tube defects (NTD), but it is uncertain whether continuing FA after the first trimester has benefits on offspring health. We aimed to evaluate the effect of FA supplementation throughout pregnancy on cognitive performance and brain function in the child. METHODS: Follow-up investigation of 11-year-old children, residing in Northern Ireland, whose mothers had participated in a randomised trial of Folic Acid Supplementation in the Second and Third Trimesters (FASSTT) in pregnancy and received 400 µg/day FA or placebo from the 14th gestational week. Cognitive performance (Full Scale Intelligence Quotient, Verbal Comprehension, Working Memory, Perceptual Reasoning, and Processing Speed) was assessed using the Wechsler Intelligence Scale for Children. Neuronal function was assessed using magnetoencephalographic (MEG) brain imaging. RESULTS: Of 119 mother-child pairs in the FASSTT trial, 68 children were assessed for neurocognitive performance at 11-year follow-up (Dec 2017 to Nov 2018). Children of mothers randomised to FA compared with placebo scored significantly higher in two Processing Speed tests, i.e. symbol search (mean difference 2.9 points, 95% CI 0.3 to 5.5, p = 0.03) and cancellation (11.3 points, 2.5 to 20.1, p = 0.04), whereas the positive effect on Verbal Comprehension was significant in girls only (6.5 points, 1.2 to 11.8, p = 0.03). MEG assessment of neuronal responses to a language task showed increased power at the Beta (13-30 Hz, p = 0.01) and High Gamma (49-70 Hz, p = 0.04) bands in children from FA-supplemented mothers, suggesting more efficient semantic processing of language. CONCLUSIONS: Continued FA supplementation in pregnancy beyond the early period currently recommended to prevent NTD can benefit neurocognitive development of the child. MEG provides a non-invasive tool in paediatric research to objectively assess functional brain activity in response to nutrition and other interventions. TRIAL REGISTRATION: ISRCTN ISRCTN19917787 . Registered on 15 May 2013.

Climate change and the dynamics of age-related malaria incidence in Southern Africa.

In the last decade, many malaria-endemic countries, like Zambia, have achieved significant reductions in malaria incidence among children <5 years old but face ongoing challenges in achieving similar progress against malaria in older age groups. In parts of Zambia, changing climatic and environmental factors are among those suspectedly behind high malaria incidence. Changes and variations in these factors potentially interfere with intervention program effectiveness and alter the distribution and incidence patterns of malaria differentially between young children and the rest of the population. We used parametric and non-parametric statistics to model the effects of climatic and socio-demographic variables on age-specific malaria incidence vis-à-vis control interventions. Linear regressions, mixed models, and Mann-Kendall tests were implemented to explore trends, changes in trends, and regress malaria incidence against environmental and intervention variables. Our study shows that while climate parameters affect the whole population, their impacts are felt most by people aged ≥5 years. Climate variables influenced malaria substantially more than mosquito nets and indoor residual spraying interventions. We establish that climate parameters negatively impact malaria control efforts by exacerbating the transmission conditions via more conducive temperature and rainfall environments, which are augmented by cultural and socioeconomic exposure mechanisms. We argue that an intensified communications and education intervention strategy for behavioural change specifically targeted at ≥5 aged population where incidence rates are increasing, is urgently required and call for further malaria stratification among the ≥5 age groups in the routine collection, analysis and reporting of malaria mortality and incidence data.

Modelling of malaria risk, rates, and trends: A spatiotemporal approach for identifying and targeting sub-national areas of high and low burden.

While mortality from malaria continues to decline globally, incidence rates in many countries are rising. Within countries, spatial and temporal patterns of malaria vary across communities due to many different physical and social environmental factors. To identify those areas most suitable for malaria elimination or targeted control interventions, we used Bayesian models to estimate the spatiotemporal variation of malaria risk, rates, and trends to determine areas of high or low malaria burden compared to their geographical neighbours. We present a methodology using Bayesian hierarchical models with a Markov Chain Monte Carlo (MCMC) based inference to fit a generalised linear mixed model with a conditional autoregressive structure. We modelled clusters of similar spatiotemporal trends in malaria risk, using trend functions with constrained shapes and visualised high and low burden districts using a multi-criterion index derived by combining spatiotemporal risk, rates and trends of districts in Zambia. Our results indicate that over 3 million people in Zambia live in high-burden districts with either high mortality burden or high incidence burden coupled with an increasing trend over 16 years (2000 to 2015) for all age, under-five and over-five cohorts. Approximately 1.6 million people live in high-incidence burden areas alone. Using our method, we have developed a platform that can enable malaria programs in countries like Zambia to target those high-burden areas with intensive control measures while at the same time pursue malaria elimination efforts in all other areas. Our method enhances conventional approaches and measures to identify those districts which had higher rates and increasing trends and risk. This study provides a method and a means that can help policy makers evaluate intervention impact over time and adopt appropriate geographically targeted strategies that address the issues of both high-burden areas, through intensive control approaches, and low-burden areas, via specific elimination programs.

Near-term climate change impacts on sub-national malaria transmission.

The role of climate change on global malaria is often highlighted in World Health Organisation reports. We modelled a Zambian socio-environmental dataset from 2000 to 2016, against malaria trends and investigated the relationship of near-term environmental change with malaria incidence using Bayesian spatio-temporal, and negative binomial mixed regression models. We introduced the diurnal temperature range (DTR) as an alternative environmental measure to the widely used mean temperature. We found substantial sub-national near-term variations and significant associations with malaria incidence-trends. Significant spatio-temporal shifts in DTR/environmental predictors influenced malaria incidence-rates, even in areas with declining trends. We highlight the impact of seasonally sensitive DTR, especially in the first two quarters of the year and demonstrate how substantial investment in intervention programmes is negatively impacted by near-term climate change, most notably since 2010. We argue for targeted seasonally-sensitive malaria chemoprevention programmes.

Environmental suitability for Aedes aegypti and Aedes albopictus and the spatial distribution of major arboviral infections in Mexico.

BACKGROUND: This paper discusses a comparative geographic distribution of Aedes aegypti and Aedes albopictus mosquitoes in Mexico, using environmental suitability modeling and reported cases of arboviral infections. METHODS: Using presence-only records, we modeled mosquito niches to show how much they influenced the distribution of Ae. aegypti and Ae. albopictus based on mosquito records collected at the municipality level. Mosquito surveillance data were used to create models regarding the predicted suitability of Ae. albopictus and Ae. aegypti mosquitos in Mexico. RESULTS: Ae. albopictus had relatively a better predictive performance (area under the curve, AUC = 0.87) to selected bioclimatic variables compared to Ae. aegypti (AUC = 0.81). Ae. aegypti were more suitable for areas with minimum temperature of coldest month (Bio6, permutation importance 28.7%) -6 °C to 21.5 °C, cumulative winter growing degree days (GDD) between 40 and 500, and precipitation of wettest month (Bio13) >8.4 mm. Minimum temperature range of the coldest month (Bio6) was -6.6 °C to 20.5 °C, and average precipitation of the wettest month (Bio13) 8.9 mm ~ 600 mm were more suitable for the existence of Ae. albopictus. However, arboviral infections maps prepared from the 2012-2016 surveillance data showed cases were reported far beyond predicted municipalities. CONCLUSIONS: This study identified the urgent necessity to start surveillance in 925 additional municipalities that reported arbovirus infections but did not report Aedes mosquito.

Combining high electron affinity and intramolecular charge transfer in 1,3-dithiole-nitrofluorene push-pull diads.

Attaching electron-rich 1,3-dithiol-2-ylidene moieties to polynitrofluorene electron acceptors leads to the formation of highly conjugated compounds 6 to 11, which combine high electron affinity with a pronounced intramolecular charge transfer (ICT) that is manifested as an intense absorption band in their visible spectra. Such a rare combination of optical and electronic properties is beneficial for several applications in optoelectronics. Thus, incorporation of fluorene-dithiole derivative 6a into photoconductive films affords photothermoplastic storage media with dramatically increased photosensitivity in the ICT region. A wide structural variation of the dithiole and fluorene parts of the molecules reveals excellent correlation between the ICT energy and the reduction potential with the Hammett's parameters for the substituents. Although only a small solvatochromism of the ICT band was observed, heating the solution led to a pronounced blueshift, which was probably as a result of increased twisting around the C9=C14 bond that links the fluorene and dithiole moieties. X-ray crystallographic analysis of 7a, 8a, 10a, 11a and 13a confirms an ICT interaction in the ground state of the molecules. The C9=C14 double bond between the donor and acceptor is substantially elongated and its length increases as the donor character of the dithiole moiety is enhanced.