Ferric Pyrophosphate Forms Soluble Iron Coordination Complexes with Zinc Compounds and Solubilizing Agents in Extruded Rice and Predicts Increased Iron Solubility and Bioavailability in Young Women.

BACKGROUND: Co-extrusion of ferric pyrophosphate (FePP) with solubilizers, citric acid/trisodium citrate (CA/TSC), or ethylenediaminetetraacetic acid (EDTA) sharply increases iron absorption. Whether this can protect against the inhibition of iron absorption by phytic acid (PA) is unclear. Sodium pyrophosphate (NaPP) may be a new enhancer of iron absorption from FePP. OBJECTIVES: Our objectives were to 1) investigate the ligand coordination of iron, zinc, and solubilizers in extruded rice and test associations with iron solubility and absorption, 2) assess whether co-extrusion of FePP + CA/TSC rice can protect against inhibition of iron absorption by PA; 3) determine the effect of zinc oxide (ZnO) compared with zinc sulfate (ZnSO4), and 4) quantify iron absorption from FePP + NaPP rice. METHODS: We produced labeled 57FePP rice cofortified with ZnSO4 and EDTA, CA/TSC or NaPP, and FePP + EDTA rice with ZnO. We used electron paramagnetic resonance (EPR) to characterize iron-ligand complexes. We measured in vitro iron solubility and fractional iron absorption (FIA) in young women (n = 21, age: 22 ± 2 y, BMI: 21.3 ± 1.5 kg/m2 geometric mean plasma ferritin, 28.5 µg/L) compared with ferrous sulfate (58FeSO4). FIA was compared by linear mixed-effect model analysis. RESULTS: The addition of zinc and solubilizers created new iron coordination complexes of Fe(III) species with a weak ligand field at a high-spin state that correlated with solubility (r2 = 0.50, P = 0.02) and absorption (r2 = 0.72, P = 0.02). Phytic acid reduced FIA from FePP + CA/TSC rice by 50% (P < 0.001), to the same extent as FeSO4. FIA from FePP + EDTA + ZnO and FePP + EDTA + ZnSO4 rice did not significantly differ. Mean FIAs from FePP + EDTA + ZnSO4, FePP + CA/TSC + ZnSO4, and FePP + NaPP + ZnSO4 rice were 9% to 11% and did not significantly differ from each other or from FeSO4. CONCLUSION: Rice extrusion of FePP with solubilizers resulted in bioavailable iron coordination complexes. In the case of FePP + CA/TSC, PA exerted similar inhibition of FIA as with FeSO4. FePP + NaPP could be a further viable solubilizing agent for rice fortification. This study was registered at clinicaltrials.gov as NCT03703739.

Aldosterone-induced microRNAs act as feedback regulators of mineralocorticoid receptor signaling in kidney epithelia.

The final steps in the Renin-Angiotensin-Aldosterone signaling System (RAAS) involve binding of the corticosteroid hormone, aldosterone to its mineralocorticoid receptor (MR). The bound MR interacts with response elements to induce or repress the transcription of aldosterone-regulated genes. A well characterized aldosterone-induced gene is the serum and glucocorticoid-induced kinase (SGK1), which acts downstream to increase sodium transport in distal kidney nephron epithelial cells. The role of microRNAs (miRs) induced by extended aldosterone stimulation in regulating MR and SGK1 has not been reported. In these studies, miRs predicted to bind to the 3'-UTR of mouse MR were profiled by qRT-PCR after aldosterone stimulation. The miR-466a/b/c/e family was upregulated in mouse kidney cortical collecting duct epithelial cells. A luciferase reporter assay confirmed miR-466 binding to both MR and SGK1 3'-UTRs. Inhibition of miR-466 increased MR and SGK1 mRNA and protein levels. Inhibiting miR-466b and preventing its upregulation after aldosterone stimulation increased amiloride-sensitive sodium transport and sensitivity to aldosterone stimulation. In vivo upregulation of miR-466 was confirmed in distal nephrons of mice on low Na+ diets. Repression of MR and SGK1 by aldosterone-induced miRs may represent a negative feedback loop that contributes to a form of aldosterone escape in vivo.

Advancing estuarine ecological forecasts: seasonal hypoxia in Chesapeake Bay.

Ecological forecasts are quantitative tools that can guide ecosystem management. The coemergence of extensive environmental monitoring and quantitative frameworks allows for widespread development and continued improvement of ecological forecasting systems. We use a relatively simple estuarine hypoxia model to demonstrate advances in addressing some of the most critical challenges and opportunities of contemporary ecological forecasting, including predictive accuracy, uncertainty characterization, and management relevance. We explore the impacts of different combinations of forecast metrics, drivers, and driver time windows on predictive performance. We also incorporate multiple sets of state-variable observations from different sources and separately quantify model prediction error and measurement uncertainty through a flexible Bayesian hierarchical framework. Results illustrate the benefits of (1) adopting forecast metrics and drivers that strike an optimal balance between predictability and relevance to management, (2) incorporating multiple data sources in the calibration data set to separate and propagate different sources of uncertainty, and (3) using the model in scenario mode to probabilistically evaluate the effects of alternative management decisions on future ecosystem state. In the Chesapeake Bay, the subject of this case study, we find that average summer or total annual hypoxia metrics are more predictable than monthly metrics and that measurement error represents an important source of uncertainty. Application of the model in scenario mode suggests that absent watershed management actions over the past decades, long-term average hypoxia would have increased by 7% compared to 1985. Conversely, the model projects that if management goals currently in place to restore the Bay are met, long-term average hypoxia would eventually decrease by 32% with respect to the mid-1980s.

In Rwandese Women with Low Iron Status, Iron Absorption from Low-Phytic Acid Beans and Biofortified Beans Is Comparable, but Low-Phytic Acid Beans Cause Adverse Gastrointestinal Symptoms.

BACKGROUND: Phytic acid (PA) is a major inhibitor of iron bioavailability from beans, and high PA concentrations might limit the positive effect of biofortified beans (BBs) on iron status. Low-phytic acid (lpa) bean varieties could increase iron bioavailability. OBJECTIVE: We set out to test whether lpa beans provide more bioavailable iron than a BB variety when served as part of a composite meal in a bean-consuming population with low iron status. METHODS: Dietary iron absorption from lpa, iron-biofortified, and control beans (CBs) (regular iron and PA concentrations) was compared in 25 nonpregnant young women with low iron status with the use of a multiple-meal crossover design. Iron absorption was measured with stable iron isotopes. RESULTS: PA concentration in lpa beans was ∼10% of BBs and CBs, and iron concentration in BBs was ∼2- and 1.5-fold compared with CBs and lpa beans, respectively. Fractional iron absorption from lpa beans [8.6% (95% CI: 4.8%, 15.5%)], BBs [7.3% (95% CI: 4.0%, 13.4%)], and CBs [8.0% (95% CI: 4.4%, 14.6%)] did not significantly differ. The total amount of iron absorbed from lpa beans and BBs was 421 µg (95% CI: 234, 756 µg) and 431 µg (95% CI: 237, 786 µg), respectively, and did not significantly differ, but was >50% higher (P < 0.005) than from CBs (278 µg; 95% CI: 150, 499 µg). In our trial, the lpa beans were hard to cook, and their consumption caused transient adverse digestive side effects in ∼95% of participants. Gel electrophoresis analysis showed phytohemagglutinin L (PHA-L) residues in cooked lpa beans. CONCLUSION: BBs and lpa beans provided more bioavailable iron than control beans and could reduce dietary iron deficiency. Digestive side effects of lpa beans were likely caused by PHA-L, but it is unclear to what extent the associated digestive problems reduced iron bioavailability. This trial was registered at clinicaltrials.gov as NCT02215278.

The inverse association between serum 25-hydroxyvitamin D and mortality may be modified by vitamin A status and use of vitamin A supplements.

BACKGROUND: Low serum 25-hydroxyvitamin D [25(OH)D] levels have been associated with higher risk of many diseases that affect mortality, including cardiovascular disease (CVD) and cancer. The inverse association between serum 25(OH)D and mortality may be modified by excess circulating vitamin A, due to interactions of vitamin A at the level of the vitamin D nuclear receptor. In this prospective cohort study, we investigated whether the association of 25(OH)D with all-cause, cancer, and CVD mortality was modified by circulating vitamin A or preformed vitamin A intake from supplements. METHODS: We analyzed 15,998 adults in the Third National Health and Nutrition Examination Survey (NHANES III), 1988-1994. Mortality data for all-cause (n = 3890), cancer (n = 844), and CVD mortality (n = 1715) were assessed through December 2006. Serum 25(OH)D was measured using a radioimmunoassay kit, vitamin A biomarkers were measured by HPLC, and information on supplement use was obtained by self-report. Multivariable hazard ratios (HRs) and corresponding 95% confidence intervals (CI) were estimated by proportional hazards regression. RESULTS: Serum 25(OH)D was significantly inversely associated with all-cause mortality (HR 0.93, 95% CI 0.89, 0.97, per 10 ng/mL increase) and also with CVD mortality and mortality due to non-cancer/non-cardiovascular causes, but not with cancer mortality. The observed inverse associations remained statistically significant only among participants with serum retinyl esters <7.0 µg/dL. High intake (>5000 IU/day) of preformed vitamin A from supplements attenuated the inverse association of 25(OH)D with overall mortality. The observed interactions were not statistically significant. CONCLUSIONS: 25(OH)D was inversely associated with overall mortality, CVD mortality, and mortality due to non-cancer/non-CVD causes, but not with cancer mortality. A possible interaction between vitamin A exposure and 25(OH)D concentration appears to be associated with an attenuation of the inverse association between risk of death and quartile of 25(OH)D concentration.

Bifidobacteria strains isolated from stools of iron deficient infants can efficiently sequester iron.

BACKGROUND: Bifidobacteria is one of the major gut commensal groups found in infants. Their colonization is commonly associated with beneficial effects to the host through mechanisms like niche occupation and nutrient competition against pathogenic bacteria. Iron is an essential element necessary for most microorganisms, including bifidobacteria and efficient competition for this micronutrient is linked to proliferation and persistence. For this research we hypothesized that bifidobacteria in the gut of iron deficient infants can efficiently sequester iron. The aim of the present study was to isolate bifidobacteria in fecal samples of iron deficient Kenyan infants and to characterize siderophore production and iron internalization capacity. RESULTS: Fifty-six bifidobacterial strains were isolated by streaking twenty-eight stool samples from Kenyan infants, in enrichment media. To target strains with high iron sequestration mechanisms, a strong iron chelator 2,2-dipyridyl was supplemented to the agar media. Bifidobacterial isolates were first identified to species level by 16S rRNA sequencing, yielding B. bifidum (19 isolates), B. longum (15), B. breve (11), B. kashiwanohense (7), B. pseudolongum (3) and B. pseudocatenulatum (1). While most isolated bifidobacterial species are commonly encountered in the infantile gut, B. kashiwanohense was not frequently reported in infant feces. Thirty strains from culture collections and 56 isolates were characterized for their siderophore production, tested by the CAS assay. Siderophore activity ranged from 3 to 89% siderophore units, with 35 strains (41%) exhibiting high siderophore activity, and 31 (36%) and 20 (23%) showing intermediate or low activity. The amount of internalized iron of 60 bifidobacteria strains selected for their siderophore activity, was in a broad range from 8 to118 µM Fe. Four strains, B. pseudolongum PV8-2, B. kashiwanohense PV20-2, B. bifidum PV28-2a and B. longum PV5-1 isolated from infant stool samples were selected for both high siderophore activity and iron internalization. CONCLUSIONS: A broad diversity of bifidobacteria were isolated in infant stools using iron limited conditions, with some strains exhibiting high iron sequestration properties. The ability of bifidobacteria to efficiently utilize iron sequestration mechanism such as siderophore production and iron internalization may confer an ecological advantage and be the basis for enhanced competition against enteropathogens.

Platensimycin is a selective FabF inhibitor with potent antibiotic properties.

Bacterial infection remains a serious threat to human lives because of emerging resistance to existing antibiotics. Although the scientific community has avidly pursued the discovery of new antibiotics that interact with new targets, these efforts have met with limited success since the early 1960s. Here we report the discovery of platensimycin, a previously unknown class of antibiotics produced by Streptomyces platensis. Platensimycin demonstrates strong, broad-spectrum Gram-positive antibacterial activity by selectively inhibiting cellular lipid biosynthesis. We show that this anti-bacterial effect is exerted through the selective targeting of beta-ketoacyl-(acyl-carrier-protein (ACP)) synthase I/II (FabF/B) in the synthetic pathway of fatty acids. Direct binding assays show that platensimycin interacts specifically with the acyl-enzyme intermediate of the target protein, and X-ray crystallographic studies reveal that a specific conformational change that occurs on acylation must take place before the inhibitor can bind. Treatment with platensimycin eradicates Staphylococcus aureus infection in mice. Because of its unique mode of action, platensimycin shows no cross-resistance to other key antibiotic-resistant strains tested, including methicillin-resistant S. aureus, vancomycin-intermediate S. aureus and vancomycin-resistant enterococci. Platensimycin is the most potent inhibitor reported for the FabF/B condensing enzymes, and is the only inhibitor of these targets that shows broad-spectrum activity, in vivo efficacy and no observed toxicity.

Microbiome-by-ethanol interactions impact Drosophila melanogaster fitness, physiology, and behavior.

The gut microbiota can affect how animals respond to ingested toxins, such as ethanol, which is prevalent in the diets of diverse animals and often leads to negative health outcomes in humans. Ethanol is a complex dietary factor because it acts as a toxin, behavioral manipulator, and nutritional source, with both direct effects on the host as well as indirect ones through the microbiome. Here, we developed a model for chronic, non-intoxicating ethanol ingestion in the adult fruit fly, Drosophila melanogaster, and paired this with the tractability of the fly gut microbiota, which can be experimentally removed. We linked numerous physiological, behavioral, and transcriptional variables to fly fitness, including a combination of intestinal barrier integrity, stored triglyceride levels, feeding behavior, and the immunodeficiency pathway. Our results reveal a complex tradeoff between lifespan and fecundity that is microbiome-dependent and modulated by dietary ethanol and feeding behavior.

Register-based information on thyroid diseases in Europe: lessons and results from the EUthyroid collaboration.

Objective: Registers of diagnoses and treatments exist in different forms in the European countries and are potential sources to answer important research questions. Prevalence and incidence of thyroid diseases are highly dependent on iodine intake and, thus, iodine deficiency disease prevention programs. We aimed to collect European register data on thyroid outcomes to compare the rates between countries/regions with different iodine status and prevention programs. Design: Register-based cross-sectional study. Methods: National register data on thyroid diagnoses and treatments were requested from 23 European countries/regions. The provided data were critically assessed for suitability for comparison between countries/regions. Sex- and age-standardized rates were calculated. Results: Register data on ≥1 thyroid diagnoses or treatments were available from 22 countries/regions. After critical assessment, data on medication, surgery, and cancer were found suitable for comparison between 9, 10, and 13 countries/regions, respectively. Higher rates of antithyroid medication and thyroid surgery for benign disease and lower rates of thyroid hormone therapy were found for countries with iodine insufficiency before approx. 2001, and no relationship was observed with recent iodine intake or prevention programs. Conclusions: The collation of register data on thyroid outcomes from European countries is impeded by a high degree of heterogeneity in the availability and quality of data between countries. Nevertheless, a relationship between historic iodine intake and rates of treatments for hyper- and hypothyroid disorders is indicated. This study illustrates both the challenges and the potential for the application of register data of thyroid outcomes across Europe.

A Household-Based Survey of Iodine Nutrition in Moroccan Children Shows Iodine Sufficiency at the National Level But Risk of Deficient Intakes in Mountainous Areas.

Historically, mountainous areas of Morocco have been affected by endemic goiter and severe iodine deficiency. In 1995, Morocco legislated salt iodization to reduce iodine deficiency. There has been no national survey of iodine nutrition in school-age children for nearly 3 decades. Our aim was to assess iodine nutrition in a national sample of 6-12-year-old children in Morocco to inform the national salt iodization strategy. In this cross-sectional household-based survey, we randomly recruited healthy 6-12-year-old children from 180 clusters in four geographic zones (north and east, central, north and south) covering the 12 regions of Morocco. A questionnaire was completed, including socio-economic status and parental level of education. In addition, anthropometric measurements were taken to assess nutrition status, and a spot urine sample was collected to measure urinary iodine concentration (UIC). A total of 3118 households were surveyed, and 1043 eligible children were recruited, 56% from urban areas and 44% from rural areas. At the national level, the percentage of surveyed samples with UIC < 50 µg/L was 21.6% (19.2%; 24.2%), which exceeds the WHO suggestion of no more than 20% of samples below 50 µg/L, despite an adequate level of median urinary iodine concentration (mUIC) at 117.4 µg/L (110.2; 123.3). There were no statistically significant differences in mUIC comparing urban vs. rural areas and socio-economic status. However, the mUIC was significantly lower in the central (high-altitude non-coastal) zone (p < 0.004), where the mUIC (95% CI) was deficient at 89.2 µg/L (80.8; 102.9). There was also a significant difference in the mUIC by head of household education level (p = 0.008). The mUIC in Moroccan children >100 µg/L indicates iodine sufficiency at the national level. However, the percentage of surveyed samples with UIC < 50 µg/L above suggests that a significant proportion of children remain at risk for iodine deficiency, and it appears those at greatest risk are residing in the central (high altitude non-coastal) zone. A national level mUIC value may conceal discrepancies in iodine intake among different sub-groups, including those defined by geographic region.

Polyphenol-rich tea decreases iron absorption from fortified wheat bread in Senegalese mother-child pairs and bioavailability of ferrous fumarate is sharply lower in children.

BACKGROUND/OBJECTIVES: Fractional iron absorption (FAFe) from ferrous fumarate (FeFum) and ferrous sulfate (FeSO4) in adults is generally comparable. While FeFum is commonly used to fortify infant foods, FAFe from FeFum in young children and infants may be decreased compared with FeSO4 and this effect has not been assessed in inhibitory vs noninhibitory meals. Previous studies also reported FAFe to be strongly correlated in mother-child pairs. Our objective was to measure FAFe from fortified bread labeled with 58FeSO4 and 57FeFum in mother-child pairs with and without a commonly consumed herbal tea of Combretum micranthum (Tisane Kinkéliba, TK). METHODS: Senegalese mother-child pairs (n = 17) were randomly assigned to receive, in a 2 × 2 factorial design, fortified bread with 58FeSO4 or 57FeFum consumed with TK or water. FAFe was assessed by measuring erythrocyte incorporation of stable iron-isotopes 14 days after administration. RESULTS: In children, relative bioavailability (RBV) from FeFum was 51 and 64% compared with FeSO4 when served with TK or water (both, P < 0.05). In mothers, the presence of TK decreased FAFe by 56% (P < 0.05) and 50% (P = 0.077) and in children by 65 and 72% (both, P < 0.0001), in the meals with 58FeSO4 and 57FeFum, respectively. After adjustment for plasma ferritin, there was a positive correlation between FAFe in mothers and children (r = 0.4142, P = 0.001). CONCLUSIONS: In Senegalese women and children, herbal tea decreased FAFe from a wheat-based meal. The RBV of FeFum was low in children but not in their mothers. FAFe was modestly correlated in mother-child pairs, possibly due to shared genetic, epigenetic or environmental background.

Comparative disposition and metabolism of paraherquamide in sheep, gerbils, and dogs.

The disposition and metabolism of paraherquamide (PHQ), a potent and broad-spectrum anthelminthic, were examined in sheep, dogs, and gerbils. The metabolism of PHQ in these species was extensive and marked by significant species differences both in vitro and in vivo. In sheep and gerbils, PHQ metabolism occurs mainly at the pyrrolidine moiety, generating several metabolites that, for the most part, retained nematodicidal activity in vitro. In dogs, the dioxepene group was also extensively metabolized, ultimately resulting in formation of a catechol and loss of pharmacological activity. After oral administration of [3H]PHQ to intact sheep, gerbils, and dogs, the majority of the administered radioactivity was recovered in feces. Intact PHQ accounted for 0% (dogs) to approximately 30% (sheep and gerbils) of drug-related material in feces. A detailed investigation of the composition of the intestinal content of sheep indicated that a significant amount of the dose was still present in the rumen 24 h after dose and that PHQ underwent significant dehydration in the cecum. The oral pharmacokinetic parameters of PHQ in sheep and dogs suggest that its absorption is rapid in both species but that its apparent elimination rate is significantly higher in the dog (t(1/2) approximately 1.5 h) than it is in sheep (t(1/2) approximately 8.5 h). The short elimination half-life and the absence of PHQ or other active components in the dog gastrointestinal tract provide a potential explanation of the lack of efficacy of PHQ in this species.

Dried Blood Spot Thyroglobulin as a Biomarker of Iodine Status in Pregnant Women.

Context: Thyroglobulin (Tg) could be a sensitive biomarker of iodine nutrition in pregnant women (PW). A dried blood spot (DBS) assay would simplify collection and transport in field studies. Objectives: Our aims were to (1) establish and test a reference range for DBS-Tg in PW; (2) determine whether co-measurement of Tg antibodies (Abs) is necessary to define population iodine status. Design, Setting, and Participants: Standardized cross-sectional studies of 3870 PW from 11 countries. For the DBS-Tg reference range, we included TgAb-negative PW (n = 599) from 3 countries with sufficient iodine intake. Main Outcome Measures: We measured the urinary iodine concentration and DBS thyroid-stimulating hormone, total thyroxin, Tg, and TgAb. Results: In the reference population, the median DBS-Tg was 9.2 µg/L (95% confidence interval, 8.7 to 9.8 µg/L) and was not significantly different among trimesters. The reference range was 0.3 to 43.5 µg/L. Over a range of iodine intake, the Tg concentrations were U-shaped. Within countries, the median DBS-Tg and the presence of elevated DBS-Tg did not differ significantly between all PW and PW who were TgAb-negative. Conclusions: A median DBS-Tg of ∼10 µg/L with <3% of values ≥44 µg/L indicated population iodine sufficiency. Concurrent measurement of TgAb did not appear necessary to assess the population iodine status.

Pulmonary pyoderma gangrenosum without cutaneous manifestations.

Pyoderma gangrenosum is a chronic sterile skin disorder that is frequently seen in association with systemic disorders such as inflammatory bowel disease. Extracutaneous pyoderma gangrenosum is rare and most commonly occurs in the lungs. It is particularly unusual for extracutaneous pyoderma gangrenosum to manifest prior to skin findings and without an associated systemic disorder. A 19-year-old white man presented with shortness of breath and a productive cough. His skin exam was normal. Unenhanced chest computed tomography showed peripheral consolidations, areas of cavitation, nodules and bilateral pleural effusions. A bronchoalveolar lavage and an autoimmune panel were unremarkable. Right lung wedge biopsies via thoracostomy was performed and showed pulmonary pyoderma gangrenosum. He was treated with corticosteroids and has returned back to his baseline. This is the first case of pulmonary pyoderma gangrenosum without any associated underlying systemic disorder and without any cutaneous manifestations to date. Serial follow-ups are necessary to assess for the development of an associated systemic disorder or skin lesions.

Care management for low-risk patients with heart failure: a randomized, controlled trial.

BACKGROUND: Nurse care management programs for patients with chronic illness have been shown to be safe and effective. OBJECTIVE: To determine whether a telephone-mediated nurse care management program for heart failure reduced the rate of rehospitalization for heart failure and for all causes over a 1-year period. DESIGN: Randomized, controlled trial of usual care with nurse management versus usual care alone in patients hospitalized for heart failure from May 1998 through October 2001. SETTING: 5 northern California hospitals in a large health maintenance organization. PATIENTS: Of 2786 patients screened, 462 met clinical criteria for heart failure and were randomly assigned (228 to intervention and 234 to usual care). INTERVENTION: Nurse care management provided structured telephone surveillance and treatment for heart failure and coordination of patients' care with primary care physicians. MEASUREMENTS: Time to first rehospitalization for heart failure or for any cause and time to a combined end point of first rehospitalization, emergency department visit, or death. RESULTS: At 1 year, half of the patients had been rehospitalized at least once and 11% had died. Only one third of rehospitalizations were for heart failure. The rate of first rehospitalization for heart failure was similar in both groups (proportional hazard, 0.85 [95% CI, 0.46 to 1.57]). The rate of all-cause rehospitalization was similar (proportional hazard, 0.98 [CI, 0.76 to 1.27]). LIMITATIONS: The findings of this study, conducted in a single health care system, may not be generalizable to other health care systems. The overall effect of the intervention was minor. CONCLUSIONS: Among patients with heart failure at low risk on the basis of sociodemographic and medical attributes, nurse care management did not statistically significantly reduce rehospitalizations for heart failure or for any cause. Such programs may be less effective for patients at low risk than those at high risk.

Iron Modulates Butyrate Production by a Child Gut Microbiota In Vitro.

UNLABELLED: The aim of this study was to investigate the effect of iron (Fe) availability on butyrate production in the complex bacterial ecosystem of the human gut. Hence, different Fe availabilities were mimicked in an in vitro colonic fermentation model (the polyfermenter intestinal model called PolyFermS) inoculated with immobilized gut microbiota from a child and in batch cultures of the butyrate producer Roseburia intestinalis. Shifts in the microbial community (16S rRNA sequencing and quantitative PCR), metabolic activity (high-performance liquid chromatography), and expression of genes involved in butyrate production were assessed. In the PolyFermS, moderate Fe deficiency resulted in a 1.4-fold increase in butyrate production and a 5-fold increase in butyryl-coenzyme A (CoA):acetate CoA-transferase gene expression, while very strong Fe deficiency significantly decreased butyrate concentrations and butyrate-producing bacteria compared with the results under normal Fe conditions. Batch cultures of R. intestinalis grown in a low-Fe environment preferentially produced lactate and had reduced butyrate and hydrogen production, in parallel with upregulation of the lactate dehydrogenase gene and downregulation of the pyruvate:ferredoxin-oxidoreductase gene. In contrast, under high-Fe conditions, R. intestinalis cultures showed enhanced butyrate and hydrogen production, along with increased expression of the corresponding genes, compared with the results under normal-Fe conditions. Our data reveal the strong regulatory effect of Fe on gut microbiota butyrate producers and on the concentrations of butyrate, which contributes to the maintenance of host gut health. IMPORTANCE: Fe deficiency is one of the most common nutritional deficiencies worldwide and can be corrected by Fe supplementation. In this in vitro study, we show that environmental Fe concentrations in a continuous gut fermentation model closely mimicking a child's gut microbiota strongly affect the composition of the gut microbiome and its metabolic activity, particularly butyrate production. The differential expression of genes involved in the butyrate production pathway under different Fe conditions and the enzyme cofactor role of Fe explain the observed modulation of butyrate production. Our data reveal that the level of dietary Fe reaching the colon affects the microbiome, and its essential function of providing the host with beneficial butyrate.

SUFFICIENT IODINE INTAKE IN SCHOOLCHILDREN FROM THE ZAGREB AREA: ASSESSMENT WITH DRIED BLOD SPOT THYROGLOBULIN AS A NEW FUNCTIONAL BIOMARKER FOR IODINE DEFICIENCY.

Current methods for assessment of iodine intake in a population comprise measurements of urinary iodine concentration (UIC), thyroid volume by ultrasound (US-Tvol), and newborn TSH. Serum or dried blood spot thyroglobulin (DBS-Tg) is a new promising functional iodine status biomarker in children. In 1996, a new act on universal salt iodination was introduced in Croatia with 25 mg of potassium iodideper kg of salt. In 2002, Croatia finally reached iodine sufficiency. However, in 2009, median UIC in 101 schoolchildren from Zagreb, the capital of Croatia, was 288 µg/L, posing to be excessive. The aim of the study was to assess iodine intake in schoolchildren from the Zagreb area and to evaluate the value of DBS-Tg in schoolchildren as a new functional biomarker of iodine deficiency (and iodine excess). The study was part of a large international study in 6- to 12-year-old children supported by UNICEF, the Swiss Federal Institute of Technology (ETH Zurich) and the International Council for the Control of Iodine Deficiency Disorders (ICCIDD). According to international study results, the median cut-off Tg < 13 µg/L and/or < 3% Tg values > 40 µg/L indicate iodine sufficiency. The study included 159 schoolchildren (median age 9.1 ± 1.4 years) from Zagreb and a nearby small town of Jastrebarsko with measurements of UIC, US-Tvol, DBS-Tg, T4, TSH and iodine content in salt from households of schoolchildren (KI/kg of salt). Overall median UIC was 205 µg/L (range 1-505 µg/L). Thyroid volumes in schoolchildren measured by US were within the normal range according to reference values. Median DBS-Tg in schoolchildren was 12.1 µg/L with 3% of Tg values > 40 µg/L. High Tg values were in the UIC range < 50 µg/L and > 300 µg/L (U-shaped curve of Tg plotted against UIC). All children were euthyroid with geometric mean TSH 0.7 ± 0.3 mU/L and arithmetic mean T4 62 ± 12.5 nmol/L. The mean KI content per kg of salt was 24.9 ± 3.1 mg/kg (range 19-36 mg/kg). Study results indicated iodine sufficiency in schoolchildren from the Zagreb area. Thyroglobulin proved to be a sensitive indicator of both iodine deficiency and iodine excess in children. Iodine content in salt from households of schoolchildren was in good compliance with the Croatian act (20-30 mg KI/kg of salt).

Subclinical Hypothyroidism and Elevated Thyroglobulin in Infants with Chronic Excess Iodine Intake.

BACKGROUND: Acute iodine excess in newborns can cause hypothyroidism, but there are limited data on the effects of iodine excess on thyroid function in older infants. The aim of this study was to measure the effects of chronic excess iodine intake on thyroid function in 6-24-month-old infants. METHODS: In this cross-sectional study, infants (n=696) in eastern Nepal were studied. Spot urine samples, venous blood samples, and household salt samples were collected, and urinary iodine concentration (UIC), serum free thyroxine (fT4), thyrotropin (TSH), thyroglobulin (Tg), and titrated household salt iodine concentration (SIC) were measured. Daily iodine intake was calculated from UIC based on estimates of urine volume at this age. RESULTS: Median (25th-75th percentile) household SIC was 89 (70-149) ppm, while national legislation stipulates a fortification level of 50 ppm. Median UIC was 407 (312-491) µg/L; 76% of infants had a UIC >300 µg/L, suggesting iodine excess. Calculated mean iodine intake in 12-24-month-old infants was 220 µg/day, exceeding the recommended safe upper limit for iodine at this age (200 µg/day). Among the infants, 15.8% had an elevated Tg, 7.4% had subclinical hypothyroidism, but <1% had overt hypothyroidism. UIC was not a significant predictor of thyroid function, thyroid hormones, or Tg. CONCLUSION: In 6-24-month-old infants exposed to excessive iodine intake, ∼7% have subclinical hypothyroidism but <1% have overt hypothyroidism. These findings suggest the thyroid in late infancy is already able to adapt to high iodine intakes and, in most cases, maintain euthyroidism.

Risks of tumor embolization in the presence of an unrecognized patent foramen ovale: case report.

A patent foramen ovale (PFO) is a fairly common septal defect in the general population. Paradoxical embolization through a PFO is a known cause of stroke. Preprocedural recognition of a PFO in a patient undergoing particulate arterial embolization can help reduce the risk of cerebral infarction.