Effects of oral iodine supplementation in very low birth weight preterm infants for the prevention of thyroid function alterations during the neonatal period: results of a randomised assessor-blinded pilot trial and neurodevelopmental outcomes at 24 months.

The trace element iodine (I) is essential for the synthesis of thyroid hormones. Parenteral nutrition solutions, formula milk, and human breast milk contain insufficient iodine to meet recommended intake for preterm infants. Iodine deficiency may affect thyroid function and may be associated with morbidity or neurological outcomes. The primary objective is to assess the evidence that dietary supplementation with iodine affects thyroid function during the neonatal period. The design was a randomised controlled pilot trial. Infants who met the inclusion criteria were enrolled through consecutive sampling and assigned to two different groups. The setting was a Spanish university hospital. Ninety-four patients with very low birth weight (under 1500 g) were included. Intervention group: 30 µg I/kg/day of iodine in oral drops given to 47 infants from their first day of life until hospital discharge. Control group: 47 infants without supplements. Formula and maternal milk samples for the determination of iodine content were collected at 1, 7, 15, 21, 30 days, and at discharge. Blood samples were collected for thyroid hormones. Neurological development was assessed at 2 years of age (Bayley III Test). Infants in the supplemented group reached the recommended levels from the first days of life. The researchers detected the effects of iodine balance on the plasma levels of thyroid hormones measured during the first 12 weeks of age. The trial assessed the impact of the intervention on neurodevelopmental morbidity.Conclusion: Thyroid function is related to iodine intake in preterm infants. Therefore, supplements should be added if iodine intake is found to be inadequate. The analyses found no effects of iodine supplementation on the composite scores for Bayley-III assessments in all major domains. The study results indicate potentially important effects on language development related to low iodine excretion during the first 4 weeks of life What is Known: • Thyroid function is related to iodine intake in preterm infants. • Preterm babies on formula preparations and with exclusive parenteral nutrition are at high risk of iodine deficiency. What is New: • Iodine intake should be monitored during the neonatal period. • Iodine supplements should be added if iodine intake is found to be inadequate.

EGFR mutation and HPV infection in sinonasal inverted papilloma and squamous cell carcinoma.

BACKGROUND: To evaluate the involvement of EGFR signalling and HPV infection in a cohort of inverted sinonasal papilloma (ISP) and sinonasal squamous cell carcinoma (SNSCC) and their value for prognosis and clinical treatment. METHODS: We analysed 55 ISP, 14 SNSCC associated with ISP (SNSCC-isp) and and 60 SNSCC not associated with ISP (SNSCC-novo) for EGFR gene mutation and copy number gain, protein expression of EGFR and phosporylated EGFR (pEGFR), and HPV-infection and KRAS mutation. Findings were correlated to clinico-pathological and follow-up data. RESULTS: We found EGFR exon 20 mutations in 38% (7/18) ISP, in 50% (6/12) SNSCC-isp and in 5% (1/19) SNSCC-novo. EGFR was expressed in 92% of ISP, while pEGFR was observed in 54% (21/39). SNSCC-isp and SNSCC-novo demonstrated comparable expression of EGFR (57% and 33%) and of pEGFR (44% and 38%). We observed an inverse relation between EGFR exon 20 mutation and pEGFR expression. Four of 39 (10%) ISP carried HPV-16. Oncogenic HPV was detected in 3/12 (25%) SNSSC-isp and in 1/8 (13%) SNSCC-novo. KRAS mutations were not detected in any of the samples. HPV infection was inversely correlated with pEGFR expression but not with EGFR mutation. ISP with EGFR activation by mutation or by phosphorylation had longer ISP-free survival, however, neither EGFR exon 20 mutation, pEGFR expression nor HPV infection demonstrated prognostic value in SNSCC. CONCLUSIONS: EGFR exon 20 mutation is frequent in ISP and SNSCC-isp, while activation of EGFR through phosphorylation also plays an important role. Our data indicate that a large proportion of SNSCC patients could benefit from therapy with modern EGFR inhibitors.

Recurrent DNA copy number alterations in intestinal-type sinonasal adenocarcinoma.

BACKGROUND: Intestinal-type sinonasal adenocarcinoma (ITAC) is a rare tumour related to occupational wood dust exposure. Few studies have described recurrent genetic changes on a genome-wide scale. The aim of this study was to obtain a high resolution map of recurrent genetic alterations in ITAC. MATERIAL AND METHODS: Copy number alterations were evaluated by microarray CGH and MLPA in 37 primary tumours. The results were correlated with pathological characteristics and clinical outcome. RESULTS: Microarray CGH identified the following recurrent aberrations, in descending order: gains at 5p15 (22 cases, 60%), 8q24 (21 cases, 57%), 20q13 (20 cases, 54%), 20q11, and 8q21 (19 cases, 51%), 20p13, and 7p11 (16 cases, 43%), and losses at 5q11-qter, 8p12-pter, and 18q12-23 (15 cases, 40%), and 17p13, and 19p13 (13 cases, 35%). MLPA analysis confirmed this global pattern of gains and losses. Chromosomal loss at 4q32-ter and gains at 1q22, 6p22 and 3q29, as well as deletion of TIMP2 and CRK correlated with unfavourable clinical outcome. CONCLUSION: ITACs have a unique pattern of chromosomal abnormalities. The four different histological subtypes of ITAC appeared genetically similar. Four chromosomal gains and losses and two specific genes showed prognostic value and may be involved in tumour progression.

[Chemical pollution and breast milk: Taking positions]. / Contaminantes químicos y lactancia materna: tomando posiciones.

Chemical pollution affects all ecosystems of our planet. Human milk has been used as a biomarker of environmental pollution as, due to bioaccumulation processes in fat tissue, many chemical compounds reach measurable concentrations that can be readily tested in breast milk. Quite frequently information about the presence of contaminants in breast milk appears in the media, leading to misunderstanding among parents and health professionals, and in some cases breastfeeding the child is stopped. In this article, the Breastfeeding Committee of the Spanish Association of Paediatrics stresses the importance of promoting breastfeeding as the healthiest option, because its benefits clearly outweigh any health risks associated with chemical contaminants in breast milk. Breast milk contains protective factors that counteract the potential effects related to prenatal exposure to environmental pollutants. This article summarises the key recommendations to reduce the level of chemical contaminants in breast milk. It also highlights the importance of government involvement in the development of programs to eliminate or reduce chemical contamination of food and the environment. In this way, the negative effects on child health resulting from exposure to these toxic compounds through the placenta and breast milk may be prevented.

Dependence on temperature and guanine-cytosine content of bubble length distributions in DNA.

We present numerical results on the temperature dependence of the distribution of bubble lengths in DNA segments of various guanine-cytosine (GC) concentrations. Base-pair openings are described by the Peyrard-Bishop-Dauxois model and the corresponding thermal equilibrium distributions of bubbles are obtained through Monte Carlo calculations for bubble sizes up to the order of a hundred base pairs. The dependence of the parameters of bubble length distribution on temperature and the GC content is investigated. We provide simple expressions which approximately describe these relations. The variation of the average bubble length is also presented. We find a temperature dependence of the exponent c that appears in the distribution of bubble lengths. If an analogous dependence exists in the loop entropy exponent of real DNA, it may be relevant to understand overstretching in force-extension experiments.

Intravitreous bevacizumab to treat subfoveal choroidal neovascularization in highly myopic eyes: short-term results.

AIM: To describe the anatomical and visual outcome of subfoveal and juxtafoveal choroidal neovascularization (CNV) in highly myopic eyes treated by intravitreal bevacizumab. METHODS: Prospective, nonrandomized, multicentric, interventional pilot study. Twenty-six highly myopic eyes from 25 patients with subfoveal and juxtafoveal CNV were treated by three monthly intravitreal injections with 1.25 mg bevacizumab. Patients were evaluated for best-corrected visual acuity (BCVA) and optical coherence tomography at baseline and then monthly. Fluorescein angiography was performed at baseline and at month 3. RESULTS: Patients averaged 49.5 years of age (SD 16.0, range 29-82). Five patients were male and 20 were female. BCVA at baseline averaged 20/62 (range 20/200-20/32) and 20/38 (range 20/160-20/20) at month 6. Average central foveal thickness was 282.4 microm (SD 68.3, range 168-447) at baseline and 224.0 microm (SD 46, range 132-294) at month 6. Fifteen eyes were naïve for treatment and 11 eyes had been previously treated by photodynamic therapy (PDT) (average 2.5 PDT sessions). Leakage from CNV had ceased in all eyes at month 3 and CNV was still closed at month 6. Neither ocular nor systemic safety issues appeared during the follow-up. CONCLUSIONS: Intravitreal bevacizumab seems to be an effective and safe therapeutic procedure to treat subfoveal and juxtafoveal CNV in highly myopic eyes. Further studies are required to verify the efficacy and usefulness of this therapy compared with established treatments for this condition.

Intravitreal bevacizumab to treat subfoveal choroidal neovascularisation in highly myopic eyes: 1-year outcome.

AIMS: The aim of the study was to examine the changes in visual acuity, fluorescein angiography (FA) and optical coherence tomography (OCT) macular thickness of subfoveal, and juxtafoveal choroidal neovascularisation (CNV) in highly myopic eyes treated by intravitreal bevacizumab. METHODS: The study was a prospective, non-randomised, multicentre, interventional case series. Twenty-nine highly myopic eyes from 28 patients with subfoveal and juxtafoveal CNV were treated by three monthly intravitreal injections of 1.25 mg bevacizumab. Patients were evaluated for best-corrected visual acuity (BCVA) and OCT at baseline and then monthly for 1 year. FA was performed at baseline, after 3 months, and whenever CNV activity was suspected. RESULTS: The average age was 50 (SD 15, range 29-82) years. The mean LogMAR BCVA at baseline was 0.55 (SD 0.25, range 0.2-1.0) and 0.38 (SD 0.32, range 0.0-1.2) at 1 year. Sixteen eyes were naïve for treatment and 13 eyes had been previously treated by photodynamic therapy (average 2.5 sessions). Leakage from CNV had ceased in all eyes at month 3. OCT central foveal thickness decreased significantly from 282 (SD 68) mum at baseline to 224 (SD 46) mum at month 12 (p = 0.008, Student t test for paired data). Six eyes needed one re-injection during follow-up at month 4 (one eye), month 6 (four eyes) and month 12 (one eye). Neither ocular nor systemic adverse reactions appeared during follow-up. CONCLUSIONS: The results of this case series suggest that intravitreal bevacizumab seems to be an effective therapeutic procedure to treat subfoveal and juxtafoveal CNV in highly myopic eyes at 1-year follow-up. Further studies are required to verify the efficacy and usefulness of this therapy compared with established treatments for this condition.

Distribution of bubble lengths in DNA.

The distribution of bubble lengths in double-stranded DNA is presented for segments of varying guanine-cytosine (GC) content, obtained with Monte Carlo simulations using the Peyrard-Bishop-Dauxois model at 310 K. An analytical description of the obtained distribution in the whole regime investigated, i.e., up to bubble widths of the order of tens of nanometers, is available. We find that the decay lengths and characteristic exponents of this distribution show two distinct regimes as a function of GC content. The observed distribution is attributed to the anharmonic interactions within base pairs. The results are discussed in the framework of the Poland-Scheraga and the Peyrard-Bishop (with linear instead of nonlinear stacking interaction) models.

Bubble nucleation and cooperativity in DNA melting.

The onset of intermediate states (denaturation bubbles) and their role during the melting transition of DNA are studied using the Peyrard-Bishop-Dauxois model by Monte Carlo simulations with no adjustable parameters. Comparison is made with previously published experimental results finding excellent agreement. Melting curves, critical DNA segment length for stability of bubbles, and the possibility of a two-state transition are studied.

Neonatal hypothyroxinemia: effects of iodine intake and premature birth.

We have investigated the effects of iodine (I) intake on urinary I excretion in preterm (PT) babies up to 2 months after birth and its effect on serum T4, free T4 (FT4), T3, TSH, and thyroglobulin (Tg) levels compared to those in term (T) newborns. Very premature and very sick infants were in negative I balance for the first weeks after birth. Later, these same infants, as well as the other PT and T newborns, were in positive balance; 75- 80% of the ingested I was not accounted for in the urine. The urinary I levels of PT and T neonates cannot be equated to their I intakes. T4, FT4, and T3 levels in PT and T neonates increased with postmenstrual age, whereas Tg decreased and TSH did not change. Serum FT4, T3, Tg, and TSH levels in PT neonates were affected negatively, independently from age, by a low I intake. PT birth also affected T4, FT4, and Tg negatively, independently from I intake and postmenstrual age, for at least 6-8 weeks after birth. Care should be taken to avoid I deficiency in PT neonates. However, even when I intake is adequate, PT newborns are hypothyroxinemic compared to T babies during an important period of brain development. This suggests the possible convenience of interventions that might mimic the intrauterine hormone environment and accelerate maturation.

Thyroid gland volume as measured by ultrasonography in preterm infants.

The volume of the thyroid gland was determined by ultrasonography in 30 preterm infants (27-36 weeks' gestation) born in Madrid. Thyroid gland volume significantly increased (p < 0.01) with postnatal and postmenstrual age and was very well correlated with body weight, height and surface area (p < 0.01). Serum thyroid hormones 3,5,3'-triiodothyronine (T3) and free thyroxine (FT4) were linearly correlated with postnatal and postmenstrual age, thus T3 and FT4 levels were also correlated with thyroid gland volume (p < 0.05). We report measurements of the thyroid gland volume obtained by ultrasonography in this group of preterm infants. Quantitative determination of thyroid gland volume is more accurate for the diagnosis of goitre than clinical criteria. It is also interesting to determine the thyroid gland volume in the neonatal period when the thyroid is particularly hypersensitive to the effects of iodine deficiency and excess.

Iodine content of infant formulas and iodine intake of premature babies: high risk of iodine deficiency.

As part of a study of thyroid function in premature babies, the iodine content of their mothers' breast milk, that of 32 formulas from different brands used in Spain, and that of 127 formulas used in other countries was determined. Breast milk contained more iodine--mean (SEM) 10 (1) microgram/dl--than most of the formulas, especially those for premature babies. Iodine intakes were therefore below the recommended daily amount (RDA) for newborns: babies of 27-30 weeks' gestational age took 3.1 (1.1) micrograms/day at 5 days of age and 29.8 (2.7) micrograms by 2 months of age. This problem is not exclusive to Spanish premature babies as the iodine content of many of the formulas on sale in other countries was also inadequate. It is concluded that preterm infants who are formula fed are at high risk of iodine deficiency.