Associations between maternal urinary iodine assessment, dietary iodine intakes and neurodevelopmental outcomes in the child: A Systematic Review

Abstract Objective Mild to moderate iodine deficiency during pregnancy has been associated with adverse neurodevelopmental outcomes in offspring. Few research studies to date combine assessment of urinary iodine (UIC and/or ICr), biomarkers that best reflect dietary intake, with reported dietary intake of iodine rich foods in their assessment of iodine deficiency. Thus, a systematic review was conducted to incorporate both these important measures. Design Using PRISMA guidelines, a comprehensive search was conducted in three electronic databases (EMBASE®, MedLine® and Web of Science®) from January 1970–March 2021. Quality assessment was undertaken using the Newcastle Ottawa Scale. Eligible studies included reported assessment of iodine status through urinary iodine (UIC and/or ICr) and/or dietary intake measures in pregnancy alongside neurodevelopmental outcomes measured in the children. Data extracted included study author, design, sample size, country, gestational age, child age at testing, cognitive tests, urinary iodine assessment (UIC in μg/L and/or ICr in μg/g), dietary iodine intake assessment and results of associations for the assessed cognitive outcomes. Results Twelve studies were included with nine reporting women as mild-moderately iodine deficient based on World Health Organization (WHO) cut-offs for urinary iodine measurements < 150 μg/l, as the median UIC value in pregnant women. Only four of the nine studies reported a negative association with child cognitive outcomes based on deficient urinary iodine measurements. Five studies reported urinary iodine measurements and dietary intakes with four of these studies reporting a negative association of lower urinary iodine measurements and dietary iodine intakes with adverse offspring neurodevelopment. Milk was identified as the main dietary source of iodine in these studies. Conclusion The majority of studies classified pregnant women to be mild-moderately iodine deficient based on urinary iodine assessment (UIC and/or ICr) and/or dietary intakes, with subsequent offspring neurodevelopment implications identified. Although a considerable number of studies did not report an adverse association with neurodevelopmental outcomes, these findings are still supportive of ensuring adequate dietary iodine intakes and urinary iodine monitoring throughout pregnancy due to the important role iodine plays within foetal neurodevelopment. This review suggests that dietary intake data may indicate a stronger association with cognitive outcomes than urinary iodine measurements alone. The strength of this review distinguishes results based on cognitive outcome per urinary iodine assessment strategy (UIC and/or ICr) with dietary data. Future work is needed respecting the usefulness of urinary iodine assessment (UIC and/or ICr) as an indicator of deficiency whilst also taking account of dietary intakes

Identification of storage conditions stabilizing extracellular vesicles pre

Extracellular vesicles (EVs) play a key role in many physiological and pathophysiological processes and hold great potential for therapeutic and diagnostic use. Despite significant advances within the last decade, the key issue of EV storage stability remains unresolved and under investigated. Here, we aimed to identify storage conditions stabilizing EVs and comprehensively compared the impact of various storage buffer formulations at different temperatures on EVs derived from different cellular sources for up to 2 years. EV features including concentration, diameter, surface protein profile and nucleic acid contents were assessed by complementary methods, and engineered EVs containing fluorophores or functionalized surface proteins were utilized to compare cellular uptake and ligand binding. We show that storing EVs in PBS over time leads to drastically reduced recovery particularly for pure EV samples at all temperatures tested, starting already within days. We further report that using PBS as diluent was found to result in severely reduced EV recovery rates already within minutes. Several of the tested new buffer conditions largely prevented the observed effects, the lead candidate being PBS supplemented with human albumin and trehalose (PBS-HAT). We report that PBS-HAT buffer facilitates clearly improved short-term and long-term EV preservation for samples stored at -80°C, stability throughout several freeze-thaw cycles, and drastically improved EV recovery when using a diluent for EV samples for downstream applications

The TNFalpha gene relates to clinical phenotype in alpha-1-antitrypsin deficiency

<p>Abstract</p> <p>Background</p> <p>Genetic variation may underlie phenotypic variation in chronic obstructive pulmonary disease (COPD) in subjects with and without alpha 1 antitrypsin deficiency (AATD). Genotype specific sub-phenotypes are likely and may underlie the poor replication of previous genetic studies. This study investigated subjects with AATD to determine the relationship between specific phenotypes and <it>TNFα </it>polymorphisms.</p> <p>Methods</p> <p>424 unrelated subjects of the PiZZ genotype were assessed for history of chronic bronchitis, impairment of lung function and radiological presence of emphysema and bronchiectasis. A subset of subjects with 3 years consecutive lung function data was assessed for decline of lung function. Four single nucleotide polymorphisms (SNPs) tagging <it>TNFα </it>were genotyped using TaqMan^®genotyping technologies and compared between subjects affected by each phenotype and those unaffected. Plasma TNFα levels were measured in all PiZZ subjects.</p> <p>Results</p> <p>All SNPs were in Hardy-Weinberg equilibrium. A significant difference in rs361525 genotype (p = 0.01) and allele (p = 0.01) frequency was seen between subjects with and without chronic bronchitis, independent of the presence of other phenotypes. TNFα plasma level showed no phenotypic or genotypic associations.</p> <p>Conclusion</p> <p>Variation in <it>TNFα </it>is associated with chronic bronchitis in AATD.</p

Socioeconomic differences in cancer survival: The Norwegian Women and Cancer Study

<p>Abstract</p> <p>Background</p> <p>Cancer survival has been observed to be poorer in low socioeconomic groups, but the knowledge about the underlying causal factors is limited. The purpose of this study was to examine how cancer survival varies by socioeconomic status (SES) among women in Norway, and to identify factors that explain this variation. SES was measured by years of education and gross household income, respectively.</p> <p>Methods</p> <p>We used data from The Norwegian Women and Cancer Study, a prospective cohort study including 91 814 women who responded to an extensive questionnaire between 1996 and 1998. A total of 3 899 incident cancer cases were diagnosed during follow-up, of whom 1 089 women died, 919 of them from cancer. Cox Proportional Hazards Model was used to calculate relative risks (RR) of mortality and 95% confidence intervals.</p> <p>Results</p> <p>We observed an overall negative socioeconomic gradient in cancer survival, which was most evident in the site specific analyses for survival of ovarian cancer by years of education. For colorectal cancer, mortality increased with years of education, but not with income. After adjustment for household size, marital status, disease stage, and smoking status the SES variation in cancer survival became non-significant. We found that the unequal socioeconomic distribution of smoking status prior to diagnosis contributed considerably to the poorer survival in low SES groups.</p> <p>Conclusion</p> <p>We found an overall negative socioeconomic gradient in cancer survival when SES is measured as years of education or gross household income. Smoking status prior to diagnosis was an important predictive factor for socioeconomic variation in survival.</p

A Comparison of Approaches to Estimate the Inbreeding Coefficient and Pairwise Relatedness Using Genomic and Pedigree Data in a Sheep Population

Genome-wide SNP data provide a powerful tool to estimate pairwise relatedness among individuals and individual inbreeding coefficient. The aim of this study was to compare methods for estimating the two parameters in a Finnsheep population based on genome-wide SNPs and genealogies, separately. This study included ninety-nine Finnsheep in Finland that differed in coat colours (white, black, brown, grey, and black/white spotted) and were from a large pedigree comprising 319 119 animals. All the individuals were genotyped with the Illumina Ovine SNP50K BeadChip by the International Sheep Genomics Consortium. We identified three genetic subpopulations that corresponded approximately with the coat colours (grey, white, and black and brown) of the sheep. We detected a significant subdivision among the colour types (FST = 5.4%, P<0.05). We applied robust algorithms for the genomic estimation of individual inbreeding (FSNP) and pairwise relatedness (ΦSNP) as implemented in the programs KING and PLINK, respectively. Estimates of the two parameters from pedigrees (FPED and ΦPED) were computed using the RelaX2 program. Values of the two parameters estimated from genomic and genealogical data were mostly consistent, in particular for the highly inbred animals (e.g. inbreeding coefficient F>0.0625) and pairs of closely related animals (e.g. the full- or half-sibs). Nevertheless, we also detected differences in the two parameters between the approaches, particularly with respect to the grey Finnsheep. This could be due to the smaller sample size and relative incompleteness of the pedigree for them

Identifying Neighborhoods of Coordinated Gene Expression and Metabolite Profiles

In this paper we investigate how metabolic network structure affects any coordination between transcript and metabolite profiles. To achieve this goal we conduct two complementary analyses focused on the metabolic response to stress. First, we investigate the general size of any relationship between metabolic network gene expression and metabolite profiles. We find that strongly correlated transcript-metabolite profiles are sustained over surprisingly long network distances away from any target metabolite. Secondly, we employ a novel pathway mining method to investigate the structure of this transcript-metabolite relationship. The objective of this method is to identify a minimum set of metabolites which are the target of significantly correlated gene expression pathways. The results reveal that in general, a global regulation signature targeting a small number of metabolites is responsible for a large scale metabolic response. However, our method also reveals pathway specific effects that can degrade this global regulation signature and complicates the observed coordination between transcript-metabolite profiles

The Role of Vaccine Coverage within Social Networks in Cholera Vaccine Efficacy

Traditional vaccine trial methods have an underlying assumption that the effect of a vaccine is the same throughout the trial area. There are, however, many spatial and behavioral factors that alter the rates of contact among infectious and susceptible individuals and result in different efficacies across a population. We reanalyzed data from a field trial in Bangladesh to ascertain whether there is evidence of indirect protection from cholera vaccines when vaccination rates are high in an individual's social network.We analyzed the first year of surveillance data from a placebo-controlled trial of B subunit-killed whole-cell and killed whole-cell-only oral cholera vaccines in children and adult women in Bangladesh. We calculated whether there was an inverse trend for the relation between the level of vaccine coverage in an individual's social network and the incidence of cholera in individual vaccine recipients or placebo recipients after controlling for potential confounding variables.Using bari-level social network ties, we found incidence rates of cholera among placebo recipients were inversely related to levels of vaccine coverage (5.28 cases per 1000 in the lowest quintile vs 3.27 cases per 1000 in the highest quintile; p = 0.037 for trend). Receipt of vaccine by an individual and the level of vaccine coverage of the individual's social network were independently related to a reduced risk of cholera.Findings indicate that progressively higher levels of vaccine coverage in bari-level social networks can lead to increasing levels of indirect protection of non-vaccinated individuals and could also lead to progressively higher levels of total protection of vaccine recipients

Design Constraints on a Synthetic Metabolism

A metabolism is a complex network of chemical reactions that converts sources of energy and chemical elements into biomass and other molecules. To design a metabolism from scratch and to implement it in a synthetic genome is almost within technological reach. Ideally, a synthetic metabolism should be able to synthesize a desired spectrum of molecules at a high rate, from multiple different nutrients, while using few chemical reactions, and producing little or no waste. Not all of these properties are achievable simultaneously. We here use a recently developed technique to create random metabolic networks with pre-specified properties to quantify trade-offs between these and other properties. We find that for every additional molecule to be synthesized a network needs on average three additional reactions. For every additional carbon source to be utilized, it needs on average two additional reactions. Networks able to synthesize 20 biomass molecules from each of 20 alternative sole carbon sources need to have at least 260 reactions. This number increases to 518 reactions for networks that can synthesize more than 60 molecules from each of 80 carbon sources. The maximally achievable rate of biosynthesis decreases by approximately 5 percent for every additional molecule to be synthesized. Biochemically related molecules can be synthesized at higher rates, because their synthesis produces less waste. Overall, the variables we study can explain 87 percent of variation in network size and 84 percent of the variation in synthesis rate. The constraints we identify prescribe broad boundary conditions that can help to guide synthetic metabolism design

Microcalcifications in breast cancer: novel insights into the molecular mechanism and functional consequence of mammary mineralisation.

BACKGROUND: Mammographic microcalcifications represent one of the most reliable features of nonpalpable breast cancer yet remain largely unexplored and poorly understood. METHODS: We report a novel model to investigate the in vitro mineralisation potential of a panel of mammary cell lines. Primary mammary tumours were produced by implanting tumourigenic cells into the mammary fat pads of female BALB/c mice. RESULTS: Hydroxyapatite (HA) was deposited only by the tumourigenic cell lines, indicating mineralisation potential may be associated with cell phenotype in this in vitro model. We propose a mechanism for mammary mineralisation, which suggests that the balance between enhancers and inhibitors of physiological mineralisation are disrupted. Inhibition of alkaline phosphatase and phosphate transport prevented mineralisation, demonstrating that mineralisation is an active cell-mediated process. Hydroxyapatite was found to enhance in vitro tumour cell migration, while calcium oxalate had no effect, highlighting potential consequences of calcium deposition. In addition, HA was also deposited in primary mammary tumours produced by implanting the tumourigenic cells into the mammary fat pads of female BALB/c mice. CONCLUSION: This work indicates that formation of mammary HA is a cell-specific regulated process, which creates an osteomimetic niche potentially enhancing breast tumour progression. Our findings point to the cells mineralisation potential and the microenvironment regulating it, as a significant feature of breast tumour development

Surgical strategies for treatment of malignant pancreatic tumors: extended, standard or local surgery?

Tumor related pancreatic surgery has progressed significantly during recent years. Pancreatoduodenectomy (PD) with lymphadenectomy, including vascular resection, still presents the optimal surgical procedure for carcinomas in the head of pancreas. For patients with small or low-grade malignant neoplasms, as well as small pancreatic metastases located in the mid-portion of pancreas, central pancreatectomy (CP) is emerging as a safe and effective option with a low risk of developing de-novo exocrine and/or endocrine insufficiency. Total pancreatectomy (TP) is not as risky as it was years ago and can nowadays safely be performed, but its indication is limited to locally extended tumors that cannot be removed by PD or distal pancreatectomy (DP) with tumor free surgical margins. Consequently, TP has not been adopted as a routine procedure by most surgeons. On the other hand, an aggressive attitude is required in case of advanced distal pancreatic tumors, provided that safe and experienced surgery is available. Due to the development of modern instruments, laparoscopic operations became more and more successful, even in malignant pancreatic diseases. This review summarizes the recent literature on the abovementioned topics