Iodine deficiency: a nutritional crisis or a matter of speculation? : the perfect discourse

During pregnancy, an increase in dietary iodine intake arises due to physiologic adaptation, a phenomenon that is characterised by complex effects that increase metabolic demands and incite hormonal changes. The presence of iodine deficiency (ID) during critical stages of gestation is associated with neurodevelopmental deficits and poses as a risk factor to the development of postpartum depression that can disrupt early mother-infant interaction. A pertinent question is at what stage of pregnancy should pregnant women be advised to take iodine-containing supplements. The narrative review aims to evaluate the recommended level of iodine supply of childbearing age, pregnant and lactating women in relation to foetal brain development and pursues to demonstrate the nutraceutical properties of seaweed as a complimentary supplement for maintaining iodine sufficiency. To achieve this, PICO was used for synthesising foreground research questions, and this was followed up by an electronic search of published data in Embase. As part of the search strategy the exclusion and inclusion criteria for eligible articles took place in Embase. To increase the variation in resources PubMed, Google Scholar, Annual Reviews and Semanticscholar were utilised. Results indicate that the dietary iodine recommendations for pregnant and lactating women are ambiguous, as they fluctuate between 150-300 μg/d and interestingly, the reference urinary iodine concentration (UIC) value of 150 µg/L is not based on direct experimental evidence; this amount is simply the best estimate for ensuring optimal iodine intake. Further observations revealed that children exposed to severe ID are liable to a 12.45 IQ points loss using the Binet or Raven Scales compared to those in iodine sufficient areas (UIC >100 µg/g UI/Cr), were the use of iodine supplementation prior to and during pregnancy could result in an 8.7 IQ point recovery. Relatedly, seaweed supplementation markedly increased urinary iodine excretion from ~266µg/d (SD:155.8) in the control group to ~567µg/d (SD:177.8, p<0.01) post consumption. Importantly these results confirm the bioavailability of iodine in seaweed. Notably, cytoarchitectural development is not exclusive to in utero and exposure to postpartum ID is associated with behavioural disorders (ADHD), learning difficulties and subtle decrements in working memory and auditory processing speed. Overall, a glut of complexities governing ID, emerging themes (dietary trends, metabolic syndrome, psycho-nutrition) and brief encounters (seaweed toxicity, processing and cooking methods) are discussed. In closing, a possible long-term indicator of iodine status is evaluated alongside the novel use of iodised food biofortification to tackle emerging micronutrient deficiencies

Iodine deficiency: a nutritional crisis or a matter of speculation? : the perfect discourse

During pregnancy, an increase in dietary iodine intake arises due to physiologic adaptation, a phenomenon that is characterised by complex effects that increase metabolic demands and incite hormonal changes. The presence of iodine deficiency (ID) during critical stages of gestation is associated with neurodevelopmental deficits and poses as a risk factor to the development of postpartum depression that can disrupt early mother-infant interaction. A pertinent question is at what stage of pregnancy should pregnant women be advised to take iodine-containing supplements. The narrative review aims to evaluate the recommended level of iodine supply of childbearing age, pregnant and lactating women in relation to foetal brain development and pursues to demonstrate the nutraceutical properties of seaweed as a complimentary supplement for maintaining iodine sufficiency. To achieve this, PICO was used for synthesising foreground research questions, and this was followed up by an electronic search of published data in Embase. As part of the search strategy the exclusion and inclusion criteria for eligible articles took place in Embase. To increase the variation in resources PubMed, Google Scholar, Annual Reviews and Semanticscholar were utilised. Results indicate that the dietary iodine recommendations for pregnant and lactating women are ambiguous, as they fluctuate between 150-300 μg/d and interestingly, the reference urinary iodine concentration (UIC) value of 150 µg/L is not based on direct experimental evidence; this amount is simply the best estimate for ensuring optimal iodine intake. Further observations revealed that children exposed to severe ID are liable to a 12.45 IQ points loss using the Binet or Raven Scales compared to those in iodine sufficient areas (UIC >100 µg/g UI/Cr), were the use of iodine supplementation prior to and during pregnancy could result in an 8.7 IQ point recovery. Relatedly, seaweed supplementation markedly increased urinary iodine excretion from ~266µg/d (SD:155.8) in the control group to ~567µg/d (SD:177.8, p<0.01) post consumption. Importantly these results confirm the bioavailability of iodine in seaweed. Notably, cytoarchitectural development is not exclusive to in utero and exposure to postpartum ID is associated with behavioural disorders (ADHD), learning difficulties and subtle decrements in working memory and auditory processing speed. Overall, a glut of complexities governing ID, emerging themes (dietary trends, metabolic syndrome, psycho-nutrition) and brief encounters (seaweed toxicity, processing and cooking methods) are discussed. In closing, a possible long-term indicator of iodine status is evaluated alongside the novel use of iodised food biofortification to tackle emerging micronutrient deficiencies

Non-communicable diseases pandemic and precision medicine: Is Africa ready?

Non-communicable diseases (NCDs) kill more than 41 million people every year, accounting for 71% of all deaths globally. The prevalence of NCDs is estimated to be higher than that of infectious diseases in Africa by 2030. Precision medicine may help with early identification of cases, resulting in timely prevention and improvement in the efficacy of treatments. However, Africa has been lagging behind in genetic research, a key component of the precision medicine initiative. A number of genomic research initiatives which could lead to translational genomics are emerging on the African continent which includes the Non-communicable Diseases Genetic Heritage Study (NCDGHS) and the Men of African Descent and Carcinoma of the Prostate (MADCaP) Network. These offer a promise that precision medicine can be applied in African countries. This review evaluates the advances of genetic studies for cancer, hypertension, type 2 diabetes and body mass index (BMI) in Africa

Hepatitis B infection is causally associated with extrahepatic cancers: A Mendelian randomization study.

BACKGROUND: Evidence from observational studies suggests that chronic hepatitis B virus (HBV) infection is associated with extrahepatic cancers. However, the causal association between chronic HBV infection and extrahepatic cancers remains to be determined. METHODS: We performed two-sample Mendelian randomization (MR) to investigate whether chronic HBV infection is causally associated with extrahepatic cancers. We identified four independent genetic variants strongly associated (P-value < 5 × 10-8) with the exposure, chronic HBV infection in 1371 cases and 2938 controls of East Asian ancestry in Korea, which were used as instrumental variables. Genome-wide association summary level data for outcome variables, that included cancer of the biliary tract, cervix, colorectum, endometrium, esophagus, gastric, hepatocellular carcinoma, lung, ovary and pancreas were obtained from Biobank Japan. FINDINGS: Using the multivariable inverse variance weighted method, we found genetic liability to chronic HBV infection causally associated with extrahepatic cancers including cervical cancer (odds ratio [OR] = 1.57, 95% confidence interval [CI] = 1.29-1.91, P-value = 0.0001) and gastric cancer (OR = 1.12, 95% CI = 1.05-1.19, P-value = 0.0001). Moreover, chronic HBV infection (OR = 1.20, 95% CI = 1.07-1.34, P-value = 0.0021) was causally associated with hepatocellular carcinoma, supporting a well-established association between chronic HBV infection and hepatocellular carcinoma. INTERPRETATION: Our MR analysis revealed that chronic HBV infection is causally associated with extrahepatic cancers including cervical and gastric cancers. FUNDING: None

Transcription-translation error: In-silico investigation of the structural and functional impact of deleterious single nucleotide polymorphisms in GULP1 gene

Nonsynonymous single nucleotide polymorphisms (nsSNPs) are one of the most common forms of mutations known to disrupt the product of translation thereby altering the protein structure-function relationship. GULP1 (PTB domain-containing engulfment adaptor protein 1) is an evolutionarily conserved adaptor protein that has been associated with glycated hemoglobin (HbA1c) in Genome-Wide Association Studies (GWAS). In order to understand the role of GULP1 in the etiology of diabetes, it is important to study some functional nsSNPs present within the GULP1 protein. We, therefore, used a SNPinformatics approach to retrieve, classify, and determine the stability effect of some nsSNPs. Y27C, G142D, A144T, and Y149C were jointly predicted by the pathogenic-classifying tools to be disease-causing, however, only G142D, A144T, and Y149C had their structural architecture perturbed as predicted by I-MUTANT and MuPro. Interestingly, G142D and Y149C occur at positions 142 and 149 of GULP1 which coincidentally are found within the binding site of GULP1. Protein-Protein interaction analysis also revealed that GULP1 interacted with 10 proteins such as Cell division cycle 5-like protein (CDC5L), ADP-ribosylation factor 6 (ARF6), Arf-GAP with coiled-coil (ACAP1), and Multiple epidermal growth factor-like domains protein 10 (MEGF10), etc. Taken together, rs1357922096, rs1264999716, and rs128246649 could be used as genetic biomarkers for the diagnosis of diabetes. However, being a computational study, these nsSNPs require experimental validation to explore their metabolic involvement in the pathogenesis of diseases

Meta-analysis of African ancestry genome-wide association studies identified novel locus and validates multiple loci associated with kidney function

Despite recent efforts to increase diversity in genome-wide association studies (GWASs), most loci currently associated with kidney function are still limited to European ancestry due to the underlying sample selection bias in available GWASs. We set out to identify susceptibility loci associated with estimated glomerular filtration rate (eGFRcrea) in 80027 individuals of African-ancestry from the UK Biobank (UKBB), Million Veteran Program (MVP), and Chronic Kidney Disease genetics (CKDGen) consortia. We identified 8 lead SNPs, 7 of which were previously associated with eGFR in other populations. We identified one novel variant, rs77408001 which is an intronic variant mapped to the ELN gene. We validated three previously reported loci at GATM-SPATA5L1, SLC15A5 and AGPAT3. Fine-mapping analysis identified variants rs77121243 and rs201602445 as having a 99.9% posterior probability of being causal. Our results warrant designing bigger studies within individuals of African ancestry to gain new insights into the pathogenesis of Chronic Kidney Disease (CKD), and identify genomic variants unique to this ancestry that may influence renal function and disease

Meta-Analysis and Multivariate GWAS Analyses in 77,850 Individuals of African Ancestry Identify Novel Variants Associated with Blood Pressure Traits

High blood pressure (HBP) has been implicated as a major risk factor for cardiovascular diseases in several populations, including individuals of African ancestry. Despite the elevated burden of HBP-induced cardiovascular diseases in Africa and other populations of African descent, limited genetic studies have been carried out to explore the genetic mechanism driving this phenomenon. We performed genome-wide association univariate and multivariate analyses of both systolic (SBP) and diastolic blood pressure (DBP) traits in 77, 850 individuals of African ancestry. We used summary statistics data from six independent cohorts, including the African Partnership for Chronic Disease Research (APCDR), the UK Biobank, and the Million Veteran Program (MVP). FUMA was used to annotate, prioritize, visualize, and interpret our findings to gain a better understanding of the molecular mechanism(s) underlying the genetics of BP traits. Finally, we undertook a Bayesian fine-mapping analysis to identify potential causal variants. Our meta-analysis identified 10 independent variants associated with SBP and 9 with DBP traits. Whilst our multivariate GWAS method identified 21 independent signals, 18 of these SNPs have been previously identified. SBP was linked to gene sets involved in biological processes such as synapse assembly and cell-cell adhesion via plasma membrane adhesion. Of the 19 independent SNPs identified in the BP meta-analysis, only 11 variants had posterior probability (PP) of > 50%, including one novel variant: rs562545 (MOBP, PP = 77%). To facilitate further research and fine-mapping of high-risk loci/variants in highly susceptible groups for cardiovascular disease and other related traits, large-scale genomic datasets are needed. Our findings highlight the importance of including ancestrally diverse populations in large GWASs and the need for diversity in genetic research

Molecular Dynamic Simulation Reveals Structure Differences in APOL1 Variants and Implication in Pathogenesis of Chronic Kidney Disease.

BACKGROUND: According to observational studies, two polymorphisms in the apolipoprotein L1 (APOL1) gene have been linked to an increased risk of chronic kidney disease (CKD) in Africans. One polymorphism involves the substitution of two amino-acid residues (S342G and I384M; known as G1), while the other involves the deletion of two amino-acid residues in a row (N388 and Y389; termed G2). Despite the strong link between APOL1 polymorphisms and kidney disease, the molecular mechanisms via which these APOL1 mutations influence the onset and progression of CKD remain unknown. METHODS: To predict the active site and allosteric site on the APOL1 protein, we used the Computed Atlas of Surface Topography of Proteins (CASTp) and the Protein Allosteric Sites Server (PASSer). Using an extended molecular dynamics simulation, we investigated the characteristic structural perturbations in the 3D structures of APOL1 variants. RESULTS: According to CASTp's active site characterization, the topmost predicted site had a surface area of 964.892 Å2 and a pocket volume of 900.792 Å3. For the top three allosteric pockets, the allostery probability was 52.44%, 46.30%, and 38.50%, respectively. The systems reached equilibrium in about 125 ns. From 0-100 ns, there was also significant structural instability. When compared to G1 and G2, the wildtype protein (G0) had overall high stability throughout the simulation. The root-mean-square fluctuation (RMSF) of wildtype and variant protein backbone Cα fluctuations revealed that the Cα of the variants had a large structural fluctuation when compared to the wildtype. CONCLUSION: Using a combination of different computational techniques, we identified binding sites within the APOL1 protein that could be an attractive site for potential inhibitors of APOL1. Furthermore, the G1 and G2 mutations reduced the structural stability of APOL1