Dietary vitamin D supplementation improves haematological status following consumption of an iron-fortified cereal: an 8-week randomised controlled trial

This article has been accepted for publication and will appear in a revised form, subsequent to peer review and/or editorial input by Cambridge University Press, in Proceedings of the Nutrition Society published by Cambridge University Press. Copyright The Authors 2020.Vitamin D, a secosteroid, has recently been implicated in the stimulation of erythroid precursors and ultimately the rate of erythropoiesis. However, there are a paucity of randomised controlled trials (RCT), investigating the effect of vitamin D supplementation iron status, especially in populations at risk of iron deficiency. An eight-week, double-blind RCT was carried out in 50 female (mean age (± SD): 27 ± 9 years), iron-deficient (plasma ferritin concentration < 20 μg/L) participants, randomised to consume an iron-fortified cereal containing 9 mg of iron, with either a vitamin D supplement (1,500 international units (IU)/day, 38 μg/day) or placebo. The effect of dietary vitamin D supplementation on haematological indicators was investigated. Blood samples were collected at baseline, 4-weeks and 8-week timepoints for measurement of iron and vitamin D status biomarkers. The effect of intervention was analysed with a mixed-model repeated measures ANOVA using IBM SPSS statistical software (Version 21, IBM Corporation, New York, USA). Significant increases were observed in two haematological parameters: haemoglobin concentration and haematocrit level from baseline to post-intervention in the vitamin D group, but not in the placebo group. The increase from baseline to post-intervention in haemoglobin concentration in the vitamin D group (135 ± 11 to 138 ± 10 g/L) was significantly higher than in the placebo group (131 ± 15 to 128 ± 13 g/L) (P ≤ 0.05). The increase in haematocrit level from baseline to post-intervention was also significantly higher in the vitamin D group (42.0 ± 3.0 to 43.8 49 ± 3.4%) compared to the placebo group (41.2 ± 4.3 to 40.7 ± 3.6%) (P ≤ 0.05). Despite non-significant changes in plasma ferritin concentration, this study demonstrates that dietary supplementation with 1,500IU vitamin D, consumed daily with an iron-fortified cereal led to improvement in haemoglobin concentration and haematocrit levels in women with low iron stores. Further long-term studies are required, however, these findings suggest a potential role for improvement of vitamin D status as an adjunct therapy for recovery of iron status in iron-deficient populations

Using microscopic video data measures for driver behavior analysis during adverse winter weather: opportunities and challenges

ABSTRACT: This paper presents a driver behavior analysis using microscopic video data measures including vehicle speed, lane-changing ratio, and time to collision. An analytical framework was developed to evaluate the effect of adverse winter weather conditions on highway driving behavior based on automated (computer) and manual methods. The research was conducted through two case studies. The first case study was conducted to evaluate the feasibility of applying an automated approach to extracting driver behavior data based on 15 video recordings obtained in the winter 2013 at three different locations on the Don Valley Parkway in Toronto, Canada. A comparison was made between the automated approach and manual approach, and issues in collecting data using the automated approach under winter conditions were identified. The second case study was based on high quality data collected in the winter 2014, at a location on Highway 25 in Montreal, Canada. The results demonstrate the effectiveness of the automated analytical framework in analyzing driver behavior, as well as evaluating the impact of adverse winter weather conditions on driver behavior. This approach could be applied to evaluate winter maintenance strategies and crash risk on highways during adverse winter weather conditions

MicroRNA-203 predicts human survival after resection of colorectal liver metastasis.

BackgroundResection of colorectal liver metastasis (CRLM) can be curative. Predicting which patients may benefit from resection, however, remains challenging. Some microRNAs (miRNAs) become deregulated in cancers and contribute to cancer progression. We hypothesized that miRNA expression can serve as a prognostic marker of survival after CRLM resection.ResultsMiR-203 was significantly overexpressed in tumors of short-term survivors compared to long-term survivors. R1/R2 margin status and high clinical risk score (CRS) were also significantly associated with short-term survival (both p = 0.001). After adjusting for these variables, higher miR-203 expression remained an independent predictor of shorter survival (p = 0.010). In the serum cohort, high CRS and KRAS mutation were significantly associated with short-term survival (p = 0.005 and p = 0.026, respectively). After adjusting for CRS and KRAS status, short-term survivors were found to have significantly higher miR-203 levels (p = 0.016 and p = 0.033, respectively).Materials and methodsWe employed next-generation sequencing of small-RNAs to profile miRNAs in solid tumors obtained from 38 patients who underwent hepatectomy for CRLM. To validate, quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was performed on 91 tumor samples and 46 preoperative serum samples.ConclusionsAfter CRLM resection, short-term survivors exhibited significantly higher miR-203 levels relative to long-term survivors. MiR-203 may serve as a prognostic biomarker and its prognostic capacity warrants further investigation

HNRNPA2B1 Is a Mediator of m6A-Dependent Nuclear RNA Processing Events

SummaryN6-methyladenosine (m6A) is the most abundant internal modification of messenger RNA. While the presence of m6A on transcripts can impact nuclear RNA fates, a reader of this mark that mediates processing of nuclear transcripts has not been identified. We find that the RNA-binding protein HNRNPA2B1 binds m6A-bearing RNAs in vivo and in vitro and its biochemical footprint matches the m6A consensus motif. HNRNPA2B1 directly binds a set of nuclear transcripts and elicits similar alternative splicing effects as the m6A writer METTL3. Moreover, HNRNPA2B1 binds to m6A marks in a subset of primary miRNA transcripts, interacts with the microRNA Microprocessor complex protein DGCR8, and promotes primary miRNA processing. Also, HNRNPA2B1 loss and METTL3 depletion cause similar processing defects for these pri-miRNA precursors. We propose HNRNPA2B1 to be a nuclear reader of the m6A mark and to mediate, in part, this mark’s effects on primary microRNA processing and alternative splicing.PaperCli

Vitamin D3 supplementation for 8 weeks leads to improved haematological status following the consumption of an iron-fortified breakfast cereal: a double-blind randomised controlled trial in iron-deficient women.

This article has been published in a revised form in British Journal of Nutrition http://doi.org/10.1017/S0007114519000412. This version is published under a Creative Commons CC-BY-NC-ND. No commercial re-distribution or re-use allowed. Derivative works cannot be distributed. © copyright holder.The effect of 38 µg (1500 IU) daily vitamin D3 supplementation, consumed with an iron-fortified breakfast cereal for 8 weeks, on haematological indicators in iron-deficient female subjects was investigated. Fifty iron-deficient subjects (plasma ferritin concentration < 20 µg/L; mean age ± SD: 27.4 ± 9.4 years) were randomised to consume an iron-fortified breakfast cereal containing 9 mg of iron daily, with either a vitamin D3 supplement or placebo. Blood samples were collected at baseline, interim (4 weeks) and post-intervention (8 weeks) for measurement of iron and vitamin D status biomarkers. The effect of intervention was analysed using mixed-model repeated measures ANOVA. Significant increases were observed in two main haematological indices: haemoglobin concentration and haematocrit level from baseline to post-intervention in the vitamin D group, but not in the placebo group. The increase from baseline to post-intervention in haemoglobin concentration in the vitamin D group (135 ± 11 to 138 ± 10 g/L) was significantly higher compared to the placebo group (131 ± 15 to 128 ± 13 g/L) (P=0.037). The increase in haematocrit level from baseline to post-intervention was also significantly higher in the vitamin D group (42.0 ± 3.0 to 43.8 ± 3.4%) compared to the placebo group (41.2 ± 4.3 to 40.7 ± 3.6%) (P=0.032). Despite the non-significant changes in plasma ferritin concentration, this study demonstrates that 38 µg supplemental vitamin D, consumed daily, with iron-fortified breakfast cereal led to improvement in haemoglobin concentration and haematocrit levels in women with low iron stores. These findings may have therapeutic implications in the recovery of iron status in iron-deficient populations at a healthcare level

Diverse receptive fields in the lateral geniculate nucleus during thalamocortical development

articles Early studies of the effects of visual deprivation demonstrated the essential role of sensory experience in the development of the highly specific connections from thalamus to visual cortex 1 . Since then, the mechanisms underlying this refinement process have been extensively investigated, and models that attempt to explain it have been proposed The receptive-field shapes of the geniculate inputs to cortex may also be important in thalamocortical development. Most models of thalamocortical development assume geniculate inputs to be a homogeneous pool of concentric, on-or off-center cells, similar to those found in the adult The maturation of retinogeniculate connections is almost certainly the mechanism for the reduction of receptive-field size in the developing LGN The final phase of retinogeniculate maturation overlaps with the critical period for thalamocortical development. In kittens, spatial receptive-field maturation in the LGN occurs during the first 2-3 weeks after eye opening 14 . The maturation of ocular dominance columns 3 and orientation selectivity 20-24 in visual cortex occur during the first few weeks after eye opening in cats and ferrets. It is thus probable that imprecise connectivity from retina to LGN at this stage influences thalamocortical development RESULTS We recorded extracellularly from 112 neurons in layers A and A1 of the lateral geniculate nucleus of the ferret: 88 neurons in immature animals at postnatal day 31-55 (P31-P55) and 24 in adults. In addition, we recorded, in the optic tract, responses of five retinal ganglion cells from P37 and P39 animals. Eyes first open on postnatal day 30-34 in the ferret 25 . Spatial structure of developing geniculate receptive fields For all cells studied, we mapped the receptive fields with a whitenoise stimulus that consisted of 16 × 16 squares (pixels), each modulated in time by a binary temporal sequence 26 . Receptivefield maps from LGN cells in adult ferrets qualitatively resembled those obtained in previous studies of the cat LGN 27 : they were concentric and had antagonistic center/surround organization Trial-to-trial robustness of receptive-field structure To ensure that the receptive fields we mapped belonged to single cells, great care was taken to verify the quality of the recordings. Only well-isolated action potentials, as assessed by online Most models of thalamocortical development in the visual system assume a homogeneous population of thalamic inputs to the cortex, each with concentric on-or off-center receptive fields. To test this, we made high-resolution spatial maps of receptive fields in the developing ferret lateral geniculate nucleus (LGN). Developing receptive fields (RFs), had a variety of shapes: some concentric, others elongated (like adult cortical receptive fields) and some with &apos;hot spots&apos; of sensitivity. These receptive fields seemed to arise from convergence of multiple retinal afferents onto LGN neurons. We present a Hebbian model whereby imprecise retinogeniculate connections help refine geniculocortical connections, sharpening both thalamocortical topography and perhaps orientation selectivity