Dostatan unos joda u školske djece s područja Zagreba: procjena određivanjem tireoglobulina u suhoj kapi krvi kao novog funkcionalnog biljega nedostatnog unosa joda

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 iodide per 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 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, DBSTg, 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 >40µg/L. High Tg values were in the UIC range 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).Metode koje se primjenjuju za procjenu unosa joda u populaciji su mjerenje izlučivanja joda mokraćom (urinary iodine concentration, UIC), procjena stanja gušavosti mjerenjem volumena štitnjače ultrazvukom (Tvol) i tireotropina (TSH) u novorođenčadi. Određivanje biljega tireoglobulina (Tg) u serumu ili suhoj kapi krvi je novi obećavajući funkcionalni biljeg stanja unosa joda u djece. Novi zakon o obveznom univerzalnom jodiranju soli uveden je u Hrvatskoj 1996. s 25 mg kalij-jodida po kilogramu soli. Hrvatska je 2002. g. postigla dostatan unos joda. Međutim, 2009. godine medijan izlučivanja joda mokraćom u školske djece iz Zagreba iznosio je 288 μg/L, što je blizu granice prekomjernog unosa joda. Cilj istraživanja bio je odrediti unos joda u školske djece s područja Zagreba i vrijednost određivanja Tg u suhoj kapi krvi u školske djece kao novog funkcionalnog biljega nedostatnog i/ili prekomjernog unosa joda. Istraživanje je dio velikog međunarnodnog projekta UNICEF-a, Švicarskog federalnog instituta tehnologije (ETH Zürich) i Međunarodnog vijeća za kontrolu poremećaja uzrokovanih nedostatkom joda (ICCIDD). Prema rezultatima međunarodnog projekta, granični prijelomni (cut-off) medijan Tg 40 µg/L upućuju na dostatan unos joda. U istraživanje je bilo uključeno 159 školske djece (medijan dobi 9,1±1,4 god.) iz Zagreba i obližnjeg gradića Jastrebarsko. Istraživanje je provedeno određivanjem UIC, Tvol, Tg u suhoj kapi krvi, T4, TSH i sadržaja joda u soli iz kućanstava školske djece (KI/kg soli). Ukupni medijan UIC iznosio je 205 µg/L (raspon 1-505 µg/L). Volumeni štitnjače u školske djece izmjereni ultrazvukom bili su unutar granica normale u usporedbi s referentnim vrijednostima. Medijan Tg u suhoj kapi krvi iznosio je u školske djece 12,1 μg/L, a 3% rezultata Tg bilo je >40 µg/L. Visoke vrijednosti Tg zabilježene su u rasponu vrijednosti UIC 300 µg/L (U-oblik krivulje Tg u odnosu na UIC). Sva djeca su bila u eutireozi s geometrijskom sredinom TSH 0,7±0,3 mU/L i aritmetičkom sredinom T4 62±12,5 nmol/L. Prosječni sadržaj kalij jodida po kg soli iznosio je 24,9±3,1 mg/kg (raspon 19-36 mg/kg). Prikazani podaci upućuju na dostatan unos joda u školske djece s područja Zagreba. Tireoglobulin je osjetljiv pokazatelj ne samo nedostatnog, nego i prekomjernog unosa joda u djece. Sadržaj joda u soli iz kućanstava školske djece bio je u skladu s hrvatskim zakonom o obveznom jodiranju soli (20-30 mg KI/kg soli)

Dostatan unos joda u školske djece s područja Zagreba: procjena određivanjem tireoglobulina u suhoj kapi krvi kao novog funkcionalnog biljega nedostatnog unosa joda

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 iodide per 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 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, DBSTg, 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 >40µg/L. High Tg values were in the UIC range 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).Metode koje se primjenjuju za procjenu unosa joda u populaciji su mjerenje izlučivanja joda mokraćom (urinary iodine concentration, UIC), procjena stanja gušavosti mjerenjem volumena štitnjače ultrazvukom (Tvol) i tireotropina (TSH) u novorođenčadi. Određivanje biljega tireoglobulina (Tg) u serumu ili suhoj kapi krvi je novi obećavajući funkcionalni biljeg stanja unosa joda u djece. Novi zakon o obveznom univerzalnom jodiranju soli uveden je u Hrvatskoj 1996. s 25 mg kalij-jodida po kilogramu soli. Hrvatska je 2002. g. postigla dostatan unos joda. Međutim, 2009. godine medijan izlučivanja joda mokraćom u školske djece iz Zagreba iznosio je 288 μg/L, što je blizu granice prekomjernog unosa joda. Cilj istraživanja bio je odrediti unos joda u školske djece s područja Zagreba i vrijednost određivanja Tg u suhoj kapi krvi u školske djece kao novog funkcionalnog biljega nedostatnog i/ili prekomjernog unosa joda. Istraživanje je dio velikog međunarnodnog projekta UNICEF-a, Švicarskog federalnog instituta tehnologije (ETH Zürich) i Međunarodnog vijeća za kontrolu poremećaja uzrokovanih nedostatkom joda (ICCIDD). Prema rezultatima međunarodnog projekta, granični prijelomni (cut-off) medijan Tg 40 µg/L upućuju na dostatan unos joda. U istraživanje je bilo uključeno 159 školske djece (medijan dobi 9,1±1,4 god.) iz Zagreba i obližnjeg gradića Jastrebarsko. Istraživanje je provedeno određivanjem UIC, Tvol, Tg u suhoj kapi krvi, T4, TSH i sadržaja joda u soli iz kućanstava školske djece (KI/kg soli). Ukupni medijan UIC iznosio je 205 µg/L (raspon 1-505 µg/L). Volumeni štitnjače u školske djece izmjereni ultrazvukom bili su unutar granica normale u usporedbi s referentnim vrijednostima. Medijan Tg u suhoj kapi krvi iznosio je u školske djece 12,1 μg/L, a 3% rezultata Tg bilo je >40 µg/L. Visoke vrijednosti Tg zabilježene su u rasponu vrijednosti UIC 300 µg/L (U-oblik krivulje Tg u odnosu na UIC). Sva djeca su bila u eutireozi s geometrijskom sredinom TSH 0,7±0,3 mU/L i aritmetičkom sredinom T4 62±12,5 nmol/L. Prosječni sadržaj kalij jodida po kg soli iznosio je 24,9±3,1 mg/kg (raspon 19-36 mg/kg). Prikazani podaci upućuju na dostatan unos joda u školske djece s područja Zagreba. Tireoglobulin je osjetljiv pokazatelj ne samo nedostatnog, nego i prekomjernog unosa joda u djece. Sadržaj joda u soli iz kućanstava školske djece bio je u skladu s hrvatskim zakonom o obveznom jodiranju soli (20-30 mg KI/kg soli)

Iron homeostasis during anemia of inflammation: a prospective study in patients with tuberculosis.

Anemia of inflammation is a hallmark of tuberculosis. Factors controlling iron metabolism during anemia of inflammation and its resolution are uncertain. Whether iron supplements should be given during anti-tuberculosis treatment to support Hb recovery is unclear. Before and during treatment of tuberculosis, we assessed iron kinetics, and changes in inflammation and iron metabolism indices. In a 26-wk prospective study, Tanzanian adults with tuberculosis (n=18) were studied before treatment and then every two weeks during treatment; oral and intravenous iron tracers were administered before treatment, after intensive phase (8/12 wk) and complete treatment (24 wk); no iron supplements were given. Before treatment, hepcidin and erythroferrone (ERFE) were greatly elevated, erythrocyte iron utilization was high (~80%) and iron absorption was negligible (<1%). During treatment, hepcidin and IL-6 decreased ~70% after only 2 wk (p<0.001); in contrast, ERFE did not significantly decrease until 8 wk (p<0.01). ERFE and IL-6 were the main opposing determinants of hepcidin (p<0.05) and greater ERFE was associated with reticulocytosis and hemoglobin (Hb) repletion (p<0.01). Dilution of baseline tracer concentration was 2.6-fold higher during intensive phase treatment (p<0.01) indicating enhanced erythropoiesis. After treatment completion, iron absorption increased ~20-fold (p<0.001); Hb increased ~25% (p<0.001). In tuberculosis-associated anemia of inflammation, our findings suggest elevated ERFE is unable to suppress hepcidin and iron absorption is negligible. During treatment, as inflammation resolves, ERFE may remain elevated, contributing to hepcidin suppression and Hb repletion. Iron is well-absorbed only after tuberculosis treatment and supplementation should be reserved for patients remaining anemic after treatment. (ClinicalTrials.gov Identifier:NCT02176772)

Computational and Experimental Characterization of RNA Cubic Nanoscaffolds

The fast-developing field of RNA nanotechnology requires the adoption and development of novel and faster computational approaches to modeling and characterization of RNA-based nano-objects. We report the first application of Elastic Network Modeling (ENM), a structure-based dynamics model, to RNA nanotechnology. With the use of an Anisotropic Network Model (ANM), a type of ENM, we characterize the dynamic behavior of non-compact, multi-stranded RNA-based nanocubes that can be used as nano-scale scaffolds carrying different functionalities. Modeling the nanocubes with our tool NanoTiler and exploring the dynamic characteristics of the models with ANM suggested relatively minor but important structural modifications that enhanced the assembly properties and thermodynamic stabilities. In silico and in vitro, we compared nanocubes having different numbers of base pairs per side, showing with both methods that the 10 bp-long helix design leads to more efficient assembly, as predicted computationally. We also explored the impact of different numbers of single-stranded nucleotide stretches at each of the cube corners and showed that cube flexibility simulations help explain the differences in the experimental assembly yields, as well as the measured nanomolecule sizes and melting temperatures. This original work paves the way for detailed computational analysis of the dynamic behavior of artificially designed multi-stranded RNA nanoparticles

Manipulation of an Innate Escape Response in Drosophila: Photoexcitation of acj6 Neurons Induces the Escape Response

Background: The genetic analysis of behavior in Drosophila melanogaster has linked genes controlling neuronal connectivity and physiology to specific neuronal circuits underlying a variety of innate behaviors. We investigated the circuitry underlying the adult startle response, using photoexcitation of neurons that produce the abnormal chemosensory jump 6 (acj6) transcription factor. This transcription factor has previously been shown to play a role in neuronal pathfinding and neurotransmitter modality, but the role of acj6 neurons in the adult startle response was largely unknown. Principal Findings: We show that the activity of these neurons is necessary for a wild-type startle response and that excitation is sufficient to generate a synthetic escape response. Further, we show that this synthetic response is still sensitive to the dose of acj6 suggesting that that acj6 mutation alters neuronal activity as well as connectivity and neurotransmitter production. Results/Significance: These results extend the understanding of the role of acj6 and of the adult startle response in general. They also demonstrate the usefulness of activity-dependent characterization of neuronal circuits underlying innat

Measurement of the cosmic ray spectrum above 4×10184{\times}10^{18} eV using inclined events detected with the Pierre Auger Observatory

A measurement of the cosmic-ray spectrum for energies exceeding $4{\times}10^{18}$ eV is presented, which is based on the analysis of showers with zenith angles greater than $60^{\circ}$ detected with the Pierre Auger Observatory between 1 January 2004 and 31 December 2013. The measured spectrum confirms a flux suppression at the highest energies. Above $5.3{\times}10^{18}$ eV, the "ankle", the flux can be described by a power law $E^{-\gamma}$ with index $\gamma=2.70 \pm 0.02 \,\text{(stat)} \pm 0.1\,\text{(sys)}$ followed by a smooth suppression region. For the energy ($E_\text{s}$) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find $E_\text{s}=(5.12\pm0.25\,\text{(stat)}^{+1.0}_{-1.2}\,\text{(sys)}){\times}10^{19}$ eV.Comment: Replaced with published version. Added journal reference and DO

Energy Estimation of Cosmic Rays with the Engineering Radio Array of the Pierre Auger Observatory

The Auger Engineering Radio Array (AERA) is part of the Pierre Auger Observatory and is used to detect the radio emission of cosmic-ray air showers. These observations are compared to the data of the surface detector stations of the Observatory, which provide well-calibrated information on the cosmic-ray energies and arrival directions. The response of the radio stations in the 30 to 80 MHz regime has been thoroughly calibrated to enable the reconstruction of the incoming electric field. For the latter, the energy deposit per area is determined from the radio pulses at each observer position and is interpolated using a two-dimensional function that takes into account signal asymmetries due to interference between the geomagnetic and charge-excess emission components. The spatial integral over the signal distribution gives a direct measurement of the energy transferred from the primary cosmic ray into radio emission in the AERA frequency range. We measure 15.8 MeV of radiation energy for a 1 EeV air shower arriving perpendicularly to the geomagnetic field. This radiation energy -- corrected for geometrical effects -- is used as a cosmic-ray energy estimator. Performing an absolute energy calibration against the surface-detector information, we observe that this radio-energy estimator scales quadratically with the cosmic-ray energy as expected for coherent emission. We find an energy resolution of the radio reconstruction of 22% for the data set and 17% for a high-quality subset containing only events with at least five radio stations with signal.Comment: Replaced with published version. Added journal reference and DO

Measurement of the Radiation Energy in the Radio Signal of Extensive Air Showers as a Universal Estimator of Cosmic-Ray Energy

We measure the energy emitted by extensive air showers in the form of radio emission in the frequency range from 30 to 80 MHz. Exploiting the accurate energy scale of the Pierre Auger Observatory, we obtain a radiation energy of 15.8 \pm 0.7 (stat) \pm 6.7 (sys) MeV for cosmic rays with an energy of 1 EeV arriving perpendicularly to a geomagnetic field of 0.24 G, scaling quadratically with the cosmic-ray energy. A comparison with predictions from state-of-the-art first-principle calculations shows agreement with our measurement. The radiation energy provides direct access to the calorimetric energy in the electromagnetic cascade of extensive air showers. Comparison with our result thus allows the direct calibration of any cosmic-ray radio detector against the well-established energy scale of the Pierre Auger Observatory.Comment: Replaced with published version. Added journal reference and DOI. Supplemental material in the ancillary file