A preliminary longitudinal study of white matter alteration in cocaine use disorder subjects

Background Previous diffusion tensor imaging (DTI) studies have consistently shown that subjects with cocaine use disorder (CocUD) had altered white matter microstructure in the corpus callosum. It is believed that these alterations are due to preexisting factors, chronic cocaine use, or both. However, there is no published longitudinal DTI study on human cocaine users yet which could shed light on the relationship between cocaine use and DTI findings. Methods This study used a longitudinal design and DTI to test if the white matter microstructure shows quicker alteration in CocUD subjects than controls. DTI data were acquired from eleven CocUD subjects who participated a treatment study and eleven non-drug-using controls at baseline (Scan 1) and after ten weeks (Scan 2). The baseline fractional anisotropy (FA), a general measure of white matter microstucture, and the change in FA (ΔFA, equals Scan 1 FA minus Scan 2 FA) were both compared between groups. Results The two groups did not show a difference in FA at baseline. The CocUD subjects had significantly greater ΔFA than the controls in the left splenium of the corpus callosum. In CocUD subjects, greater ΔFA in this region was associated with shorter lifetime cocaine use and greater number of positive cocaine urine samples collected during the treatment. Conclusion The finding in the left splenium is consistent with previous animal studies and provide indirect evidence about the effects of chronic cocaine use on white matter alterations. The subject sample size is small, therefore the results should be treated as preliminary

Projected health effects of realistic dietary changes to address freshwater constraints in India : a modelling study

Acknowledgements This study forms part of the Sustainable and Healthy Diets in India project supported by the Wellcome Trust's Our Planet, Our Health programme (grant number 103932). LA's PhD is funded by the Leverhulme Centre for Integrative Research on Agriculture and Health. SA is supported by a Wellcome Trust Capacity Strengthening Strategic Award-Extension phase (grant number WT084754/Z/08/A). We would like to thank Zaid Chalabi (London School of Hygiene & Tropical Medicine) for providing valuable guidance on the modelling methods.Peer reviewedPublisher PD

Inflammation Adjustment by Two Methods Decreases the Estimated Prevalence of Zinc Deficiency in Malawi.

Serum zinc concentration (SZC) is used widely to assess population-level zinc status. Its concentration decreases during inflammatory responses, which can affect the interpretation of the results. This study aimed to re-estimate the prevalence of zinc deficiency in Malawi based on the 2015-2016 Malawi Micronutrient Survey (MNS) data, by adjusting SZC measures with markers of inflammation. SZC and inflammation data from 2760 participants were analysed. Adjustments were made using: (1) The Internal Correction Factor (ICF) method which used geometric means, and (2) The Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) method, which used linear regression. Mean SZC values increased significantly when adjustments were made by either ICF or BRINDA (p < 0.001). The national prevalence of zinc deficiency decreased from 62% to 59%, after ICF adjustment, and to 52% after BRINDA adjustment. ICF and BRINDA values of SZC were highly correlated (p < 0.001, r = 0.99), but a Bland-Altman plot showed a lack of agreement between the two methods (bias of 2.07 µg/dL). There was no association between the adjusted SZC and stunting, which is a proxy indicator for zinc deficiency. Inflammation adjustment of SZC, using ICF or BRINDA, produces lower estimates of zinc deficiency prevalence, but the lack of agreement between the adjustment methods warrants further research. Furthermore, the lack of association between SZC and stunting highlights the need to explore other biomarkers and proxies of population zinc assessment. This study demonstrates the importance of considering inflammatory confounders when reporting SZC, to ensure accuracy and to support policy decision making

Limited Supply of Protein and Lysine Is Prevalent among the Poorest Households in Malawi and Exacerbated by Low Protein Quality

We estimated dietary supplies of total and available protein and indispensable amino acids (IAAs) and predicted the risk of deficiency in Malawi using Household Consumption and Expenditure Survey data. More than half of dietary protein was derived from cereal crops, while animal products provided only 11%. The supply of IAAs followed similar patterns to that of total proteins. In general, median protein and IAA supplies were reduced by approximately 17% after accounting for digestibility, with higher losses evident among the poorest households. At population level, 20% of households were at risk of protein deficiency due to inadequate available protein supplies. Of concern was lysine supply, which was inadequate for 33% of households at the population level and for the majority of the poorest households. The adoption of quality protein maize (QPM) has the potential to reduce the risk of protein and lysine deficiency in the most vulnerable households by up to 12% and 21%, respectively

Effectiveness of Agronomic Biofortification Strategy in Fighting against Hidden Hunger

Micronutrient deficiencies (MNDs), also known as hidden hunger, affect more than a quarter of the global population. Agronomic biofortification helps to increase the concentration of a target mineral in food crops and improve human mineral dietary intake. It is a means of providing nutrient-dense foods to a larger population, especially among rural resource-poor settings, providing that they have access to mineral fertilizers. However, the feasibility of agronomic biofortification in combating hidden hunger depends on several factors in addition to fertilizer access, including crop type, genotype, climate, soils, and soil mineral interactions. Consideration of its effectiveness in increasing human mineral intake to the daily requirements and the improvement of human health and the cost-effectiveness of the program is also important. In this paper, we review the available literature regarding the potential effectiveness and challenges of agronomic biofortification to improve crop micronutrient concentrations and reduce hidden hunger

Site-specific factors influence the field performance of a Zn-biofortified wheat variety

Background: Biofortification of wheat with zinc (Zn) through breeding and agronomy can reduce Zn deficiencies and improve human health. ‘High-Zn’ wheat varieties have been released in India and Pakistan, where wheat is consumed widely as a dietary staple. The aim of this study was to quantify the potential contribution of a ‘high-Zn’ wheat variety (Triticum aestivum L. var. Zincol-2016) and Zn fertilisers to improving dietary Zn supply under field conditions in Pakistan. Methods: Grain Zn concentration of Zincol-2016 and local reference varieties were determined at three sites of contrasting soil Zn status: Faisalabad (Punjab Province; diethylenetriamine pentaacetate- (DTPA-)extractable Zn, 1.31 mg kg-1 soil; gross plot size 13.3 m2; n=4; reference var. Faisalabad-2008), Islamabad (Capital Territory; 0.48 mg kg-1; 4.6 m2; n=5; reference var. NARC-2011), and Pir Sabak (Khyber Pakhtunkhwa, KPK, Province; 0.12 mg kg-1 soil; 9.1 m2; n=4; reference vars. Pirsabak-2015, Wadhan-2017). Eight Zn fertiliser treatment levels were tested using a randomised complete block design: control; soil (5 or 10 kg ha-1 ZnSO4.H2O; 33% Zn applied at sowing); foliar (0.79 or 1.58 kg of ZnSO4.H2O ha-1 applied as a 250 L ha-1 drench at crop booting stage); three soil foliar combinations. Results: At the Faisalabad site, the grain Zn concentration of Zincol-2016 was greater than Faisalabad-2008, with no yield penalty. Zincol-2016 did not have larger grain Zn concentrations than reference varieties used at Islamabad or Pir Sabak sites, which both had a lower soil Zn status than the Faisalabad site. Foliar Zn fertilisation increased grain Zn concentration of all varieties at all sites. There were no significant effects of soil Zn fertilisers, or variety·fertiliser interactions, on grain Zn concentration or yield. Conclusions: Environment and management affect the performance of ‘high-Zn’ wheat varieties, and these factors needs to be evaluated at scale to assess the potential nutritional impact of Zn biofortified crops. Designing studies to detect realistic effect sizes for new varieties and crop management strategies is therefore an important consideration. The current study indicated that nine replicate plots would be needed to achieve 80% power to detect a 25% increase in grain Zn concentration

A surface groove essential for viral Bcl-2 function during chronic infection in vivo

Antiapoptotic Bcl-2 family proteins inhibit apoptosis in cultured cells by binding BH3 domains of proapoptotic Bcl-2 family members via a hydrophobic BH3 binding groove on the protein surface. We investigated the physiological importance of the BH3 binding groove of an antiapoptotic Bcl-2 protein in mammals in vivo by analyzing a viral Bcl-2 family protein. We show that the gamma-herpesvirus 68 (gammaHV68) Bcl-2 family protein (gammaHV68 v-Bcl-2), which is known to inhibit apoptosis in cultured cells, inhibits both apoptosis in primary lymphocytes and Bax toxicity in yeast. Nuclear magnetic resonance determination of the gammaHV68 v-Bcl-2 structure revealed a BH3 binding groove that binds BH3 domain peptides from proapoptotic Bcl-2 family members Bax and Bak via a molecular mechanism shared with host Bcl-2 family proteins, involving a conserved arginine in the BH3 peptide binding groove. Mutations of this conserved arginine and two adjacent amino acids to alanine (SGR to AAA) within the BH3 binding groove resulted in a properly folded protein that lacked the capacity of the wild-type gammaHV68 v-Bcl-2 to bind Bax BH3 peptide and to block Bax toxicity in yeast. We tested the physiological importance of this v-Bcl-2 domain during viral infection by engineering viral mutants encoding a v-Bcl-2 containing the SGR to AAA mutation. This mutation resulted in a virus defective for both efficient reactivation of gammaHV68 from latency and efficient persistent gammaHV68 replication. These studies demonstrate an essential functional role for amino acids in the BH3 peptide binding groove of a viral Bcl-2 family member during chronic infection

The potential of spot urine as a biomarker for zinc assessment in Malawian children and adults

Population-level assessment of zinc deficiency remains a challenge due to the lack of suitable biomarkers. Spot urinary zinc concentration (UZC) has the potential to provide information on population zinc status in large-scale surveys, but there is no established cut-off point indicating deficiency. A strong correlation between this biomarker and an established biomarker such as serum zinc concentration (SZC) in paired samples (i.e., from the same individual), could identify the thresholds indicating zinc deficiency. This study, therefore, aimed to regress spot UZC from school-aged children and women from the Malawi micronutrient survey with paired SZC data using a linear mixed-effects model. The nested variance components indicated no linear relationship between the UZC and SZC data, irrespective of adjustments for inflammation and hydration. Thresholds of urinary zinc excretion that have been suggested by expert panels were applied to the spot UZC data, as a post-hoc analysis. The zinc deficiency prevalence estimates derived from these suggested thresholds were not similar to the estimates from the SZC data, and further research is required to understand whether spot UZC can still provide useful information in population zinc assessment

Community Perceptions of Zinc Biofortified Flour during an Intervention Study in Pakistan

Zinc-biofortified flour may be a cost-effective approach to improve zinc status of populations in low-resource settings. The success of biofortification programmes is subject to acceptability and uptake by consumers. This study explored community leaders’ and community members’ (n = 72) experiences and attitudes towards the flour provided during a cluster randomised controlled trial of zinc biofortified wheat in rural Pakistan (BiZiFED2). Focus group discussions (n = 12) were conducted and thematic analysis applied using an inductive, semantic, contextualist approach. Five themes were identified: (1) Contribution to food security; (2) Better sensory and baking properties than local flour; (3) Perceived health benefits; (4) Willingness to pay for the flour; and (5) Importance of trusted promoters/suppliers. Although the participants were blind to whether they had received control or biofortified flour, referred to collectively as “study flour”, the results indicated that the study flour performed well in terms of its taste and bread making qualities, with no adverse reports from participants in either arm of the BIZIFED2 RCT. Participants suggested that they would buy the biofortified wheat if this was available at a fair price due to perceived health benefits, reporting positive sensory characteristics and cooking attributes when compared to the flour available in the local markets. Overall, there was a positive reception of the programme and flour among the participants, and members of the community hoped for its continuation and expansion

The BiZiFED project: Biofortified Zinc Flour to Eliminate Deficiency in Pakistan

Zinc deficiency is a global public health problem, affecting ~17% of the world’s population, with the greatest burden in low and middle-income countries. An increasing body of evidence suggests that biofortification may be a cost-effective and sustainable approach to reducing zinc and other micronutrient deficiencies. Biofortification enhances the nutritional quality of food crops through conventional plant breeding techniques and agronomic practices. This paper presents our ongoing research on biofortification in Pakistan, where over 40% of women are zinc deficient. The Biofortified Zinc Flour to Eliminate Deficiency (BiZiFED) project aims to investigate the impact of biofortification as a strategy to alleviate zinc deficiency in Pakistan. The project is supported by the Biotechnology and Biological Sciences Research Council (BBSRC) Global Challenges Research Fund from May 2017 to April 2019. This paper outlines the four objectives and work packages within the BiZiFED project: 1) a doubleblind, randomised controlled trial to examine the effect of consuming flour made from a high zinc variety of biofortified wheat (Zincol- 2016/NR-421) on dietary zinc intake and status; 2) a cost-effectiveness study to assess the health and economic impact of agronomic biofortification of wheat; 3) a mixed methods study to explore the cultural acceptability and sustainability of biofortification in Pakistan; 4) capacity building and development of long-term research partnerships in Pakistan. The findings will contribute to the evidence base for the potential impact of biofortification to alleviate zinc deficiency among the poorest communities