Testing quantum electrodynamics in extreme fields using helium-like uranium.

Quantum electrodynamics (QED), the quantum field theory that describes the interaction between light and matter, is commonly regarded as the best-tested quantum theory in modern physics. However, this claim is mostly based on extremely precise studies performed in the domain of relatively low field strengths and light atoms and ions1-6. In the realm of very strong electromagnetic fields such as in the heaviest highly charged ions (with nuclear charge Z ≫ 1), QED calculations enter a qualitatively different, non-perturbative regime. Yet, the corresponding experimental studies are very challenging, and theoretical predictions are only partially tested. Here we present an experiment sensitive to higher-order QED effects and electron-electron interactions in the high-Z regime. This is achieved by using a multi-reference method based on Doppler-tuned X-ray emission from stored relativistic uranium ions with different charge states. The energy of the 1s1/22p3/2 J = 2 → 1s1/22s1/2 J = 1 intrashell transition in the heaviest two-electron ion (U90+) is obtained with an accuracy of 37 ppm. Furthermore, a comparison of uranium ions with different numbers of bound electrons enables us to disentangle and to test separately the one-electron higher-order QED effects and the bound electron-electron interaction terms without the uncertainty related to the nuclear radius. Moreover, our experimental result can discriminate between several state-of-the-art theoretical approaches and provides an important benchmark for calculations in the strong-field domain.

Toward the development of sensors for lung cancer: The adsorption of 1-propanol on hydrophobic zeolites.

A healthy breath is mainly composed of water, carbon dioxide, molecular nitrogen, and oxygen and it contains many species, in small quantities, which are related to the ambient atmosphere and the metabolism. The breath of a person affected by lung cancer presents a concentration of 1-propanol higher than usual. In this context, the development of specific sensors to detect 1-propanol from breath is of high interest. The amount of propanol usually detected on the breath is of few ppb; this small quantity is a handicap for a reliable diagnostic. This limitation can be overcome if the sensor is equipped with a pre-concentrator. Our studies aim to provide an efficient material playing this role. This will contribute to the development of reliable and easy to use lung cancer detectors. For this, we investigate the properties of a few hydrophobic porous materials (chabazite, silicalite-1, and dealuminated faujasite). Hydrophobic structures are used to avoid saturation of materials by the water present in the exhaled breath. Our experimental and simulation results suggest that silicalite -1 (MFI) is the most suitable structure to be used as a pre-concentrator.

Stochastic epigenetic mutations as possible explanation for phenotypical discordance among twins with congenital hypothyroidism.

PURPOSE: The elevated frequency of discordance for congenital hypothyroidism (CH) phenotype between monozygotic twins suggests the involvement of non-mendelian mechanisms. The aim of the study was to investigate the role of epigenetics in CH pathogenesis. METHODS: A genome-wide DNA methylation analysis was performed on the peripheral blood of 23 twin pairs (10 monozygotic and 13 dizygotic), 4 concordant and 19 discordant pairs for CH at birth. RESULTS: Differential methylation analysis did not show significant differences in methylation levels between CH cases and controls, but a different methylation status of several genes may explain the CH discordance of a monozygotic twin couple carrying a monoallelic nonsense mutation of DUOX2. In addition, the median number of hypo-methylated Stochastic Epigenetic Mutations (SEMs) resulted significantly increased in cases compared to controls. The prioritization analysis for CH performed on the genes epimutated exclusively in the cases identified SLC26A4, FOXI1, NKX2-5 and TSHB as the genes with the highest score. The analysis of significantly SEMs-enriched regions led to the identification of two genes (FAM50B and MEG8) that resulted epigenetically dysregulated in cases. CONCLUSION: Epigenetic modifications may potentially account for CH pathogenesis and explain discordance among monozygotic twins.

Autoimmune polyendocrine syndrome type 1: an Italian survey on 158 patients.

BACKGROUND: Autoimmune Polyglandular Syndrome type 1 (APS-1) is a rare recessive inherited disease, caused by AutoImmune Regulator (AIRE) gene mutations and characterized by three major manifestations: chronic mucocutaneous candidiasis (CMC), chronic hypoparathyroidism (CH) and Addison's disease (AD). METHODS: Autoimmune conditions and associated autoantibodies (Abs) were analyzed in 158 Italian patients (103 females and 55 males; F/M 1.9/1) at the onset and during a follow-up of 23.7 ± 15.1 years. AIRE mutations were determined. RESULTS: The prevalence of APS-1 was 2.6 cases/million (range 0.5-17 in different regions). At the onset 93% of patients presented with one or more components of the classical triad and 7% with other components. At the end of follow-up, 86.1% had CH, 77.2% AD, 74.7% CMC, 49.5% premature menopause, 29.7% autoimmune intestinal dysfunction, 27.8% autoimmune thyroid diseases, 25.9% autoimmune gastritis/pernicious anemia, 25.3% ectodermal dystrophy, 24% alopecia, 21.5% autoimmune hepatitis, 17% vitiligo, 13.3% cholelithiasis, 5.7% connective diseases, 4.4% asplenia, 2.5% celiac disease and 13.9% cancer. Overall, 991 diseases (6.3 diseases/patient) were found. Interferon-ω Abs (IFNωAbs) were positive in 91.1% of patients. Overall mortality was 14.6%. The AIRE mutation R139X was found in 21.3% of tested alleles, R257X in 11.8%, W78R in 11.4%, C322fsX372 in 8.8%, T16M in 6.2%, R203X in 4%, and A21V in 2.9%. Less frequent mutations were present in 12.9%, very rare in 9.6% while no mutations in 11% of the cases. CONCLUSIONS: In Italy, APS-1 is a rare disorder presenting with the three major manifestations and associated with different AIRE gene mutations. IFNωAbs are markers of APS-1 and other organ-specific autoantibodies are markers of clinical, subclinical or potential autoimmune conditions.

The use of online video consultations in the aftercare of orthopedic patients: a prospective case-control study.

BACKGROUND: Video consultations have proven to be an efficient source of support for patient-doctor interactions and have become increasingly used in orthopedics, especially during the COVID-19 pandemic. This study analyzed both patients' and doctors' acceptance of an orthopedic telemedical consultation (OTC) and compared the results of OTC examinations to the results of live consultation (LC) to identify discrepancies. METHODS: The study was carried out in an orthopedic department of a German hospital between 2019 and 2020. After written informed consent was obtained, patients voluntarily presented for follow-up by OTC and LC. The experience with and attitudes toward OTC among both patients and doctors was evaluated (using Likert scale-scored and open questions, 26 to 28 items). The results of the OTC and LC examinations were compared using a 12-item checklist. The data were analyzed by quantitative and qualitative statistics. RESULTS: A total of 53 patients were included, each of whom completed an OTC and an LC. The OTC was rated as pleasant, and the experience was rated as very satisfying (average rating on a 5-point Likert scale, with 1 indicating strong agreement: doctors: 1.2; patients: 1.3). Various technical and organizational challenges were identified. Compared to LC, OTC showed no significant differences in patient history or in inspection, palpation, or active range of motion results. Only for the functional or passive joint assessment did LC show significantly higher suitability (p < 0.05) than OTC. Recommendations for further procedures did not differ significantly between OTC and LC. CONCLUSIONS: Because of the high acceptance and the objective benefits of OTC and the similarity of clinical results with LC, OTC is recommendable for orthopedic follow-up examinations. To better assess joint functionality, meaningful digital alternatives for established examination methods should be further investigated.

"Block-and-replace" treatment in Graves' disease: experience in a cohort of pediatric patients.

PURPOSE: The "block-and-replace" (BR) method involves the use of a high dose of antithyroid drugs (ATD) with levothyroxine (L-T4). Its use in the management of Graves' disease (GD) is still debated mainly because the frequency of side effects of ATD is dose dependent. We retrospectively studied the effect of medium dose of ATD with L-T4 versus monotherapy with ATD in pediatric patients with unstable GD. METHODS: 28 pediatric patients with GD with unstable response to ATD were treated with L-T4 and medium dose of ATD. We compared the rate of euthyroidism, hypothyroidism and hyperthyroidism episodes observed during treatment with methimazole alone with those observed during the BR approach. We evaluated the occurrence of side effects and the rate of remission in patients treated with ATD + L-T4 therapy and the efficacy of combination therapy to postpone a definitive treatment (radioiodine and thyroidectomy). RESULTS: Patients showed a better control of thyroid function during the BR therapy, presenting fewer episodes of hyperthyroidism and hypothyroidism. No serious side effects during the BR approach were observed. Only one patient went into remission with the ATD + L-T4 therapy. Fifteen patients required a definitive therapy (4 radioiodine, 11 thyroidectomy). The use of BR method has delayed radioiodine treatment for 4.9 years and surgery for 2.9 years. CONCLUSIONS: The BR method does not increase the remission rates. It may be useful to combine L-T4 with a medium dose of methimazole when GD is difficult to manage with methimazole alone. It may represent a therapeutic option to postpone definitive treatments to a suitable age.

Reduced leadset selection and performance evaluation in the inverse problem of electrocardiography for reconstructing the ventricularly paced electrograms.

OBJECTIVE: Noninvasive electrocardiographic imaging (ECGI) is used for obtaining high-resolution images of the electrical activity of the heart, and is a powerful method with the potential to detect certain arrhythmias. However, there is no 'best' lead configuration in the literature to measure the torso potentials. This paper evaluates ECGI reconstructions using various reduced leadset configurations, explores whether one can find a common reduced leadset configuration that can accurately reconstruct the electrograms for datasets with different pacing sites, and compares two activation time estimation methods. APPROACH: We used 23 ventricularly-paced datasets with pacing sites on different regions of the epicardium. Starting with a full 192­leadset, we found "optimized" reduced leadsets specific to each dataset; we considered 64­lead and 32­lead configurations. Based on the histogram of individual "optimized" lead selections, we found a common reduced leadset. We compared the ECGI reconstructions and activation times of the individually optimized lead configurations with the common lead configurations. RESULTS: Both 64­lead configurations had similar performances to the 192­leadset. 32­leadset configurations, on the other hand, yielded noisy reconstructions, which affected their performance. SIGNIFICANCE: There are no statistically significant differences in the performance of the inverse solutions when a 64­lead common reduced leadset is used to estimate the electrograms and their respective pacing sites compared to using the full leadset. 32­lead configurations, on the other hand, require a more careful study to improve their performance. The activation time method used significantly affects the pacing site estimation performance, especially with fewer electrodes.

The association between challenging behaviour and symptoms of post-traumatic stress disorder in people with intellectual disabilities: a Bayesian mediation analysis approach.

BACKGROUND: A preponderance of behavioural symptoms is assumed to be the main difference in the manifestation of symptoms of post-traumatic stress disorder (PTSD) in people with intellectual disability (ID). However, no study so far has assessed the relationship between challenging behaviour (CB) and PTSD. The present study aims to explore this relationship by exploring whether CB is directly related to trauma exposure or whether this relationship is mediated through core symptoms of PTSD. METHODS: Trauma exposure and current symptoms of PTSD were assessed in 43 adults with mild to moderate ID. Parallel versions were administered to 43 caregivers, including the Aberrant Behaviour Checklist to measure CB. Bayesian mediation analyses were conducted using self-rated and informant-rated data. RESULTS: The self-report data showed no associations of CB with trauma exposure or PTSD symptoms. The association between informant-rated trauma exposure and irritability was mediated by severity and frequency of PTSD symptoms. The associations between informant-reported trauma exposure and the Aberrant Behaviour Checklist subscales hyperactivity and inappropriate speech were mediated by PTSD symptom severity. CONCLUSIONS: The relationship between trauma exposure and CB was mediated by PTSD symptoms. PTSD core symptoms should be considered as underlying causes of CB, highlighting the necessity to explore trauma biography and symptoms of PTSD. The improvement of self-report assessment in people with ID is an important task for future studies.

Magma Degassing as a Source of Long-Term Seismicity at Volcanoes: The Ischia Island (Italy) Case.

Transient seismicity at active volcanoes poses a significant risk in addition to eruptive activity. This risk is powered by the common belief that volcanic seismicity cannot be forecast, even on a long term. Here we investigate the nature of volcanic seismicity to try to improve our forecasting capacity. To this aim, we consider Ischia volcano (Italy), which suffered similar earthquakes along its uplifted resurgent block. We show that this seismicity marks an acceleration of decades-long subsidence of the resurgent block, driven by degassing of magma that previously produced the uplift, a process not observed at other volcanoes. Degassing will continue for hundreds to thousands of years, causing protracted seismicity and will likely be accompanied by moderate and damaging earthquakes. The possibility to constrain the future duration of seismicity at Ischia indicates that our capacity to forecast earthquakes might be enhanced when seismic activity results from long-term magmatic processes, such as degassing.

Tolerance evaluation of overdosed dietary levels of 25-hydroxyvitamin D3 in growing piglets.

Forty-eight, cross-bred (GL × LW × P) piglets were used in a 42-day tolerance trial to assess the effects of feeding diets supplemented with vitamin D or increasing levels of 25-hydroxyvitamin D3 (25-OH-D3 ). Six-week-old piglets (24 castrate males, 24 females) were used. Two replicate groups of 6 piglets were randomized by weight and allocated to four dietary treatments. The control group (T1) was supplemented with 50 µg vitamin D3 /kg feed. The experimental groups received 25-OH-D3 at the recommended dose (T2: 50 µg/kg = 1x), at 250 µg/kg (T3: 5x) or at 500 µg/kg (T4: 10x) respectively. Feed intake and daily weight gain were measured weekly, and the animals were examined by a veterinarian daily. After 42 days, body mass, blood, urine, bone and tissue samples were analysed and a pathology examination conducted. Dietary treatments had no significant effect on final body mass or daily weight gain. The 25-OH-D3 plasma concentration in T1 was 17 ± 3 ng/ml (mean ± SD) while the respective values of the experimental groups were significantly increased in T2, T3 and T4. Tissue concentrations of 25-OH-D3 were higher in liver and muscle for T3 and T4 and in skin for T4 than in T1. However, neither gross pathology nor histology, nor blood and urine characteristics, nor bone parameters were affected by dietary treatments. Weight of organs as well as dry matter, ash and calcium content of kidneys remained unaffected by dietary 25-OH-D3 intake. Furthermore, no changes were observed for general indicators of health. The results of this study demonstrated that feeding piglets with 25-OH-D3 at 5 or 10 times the recommended level had no adverse effects on any of the biological parameters measured. It was concluded that 25-OH-D3 can be regarded as a supplement with a very high safety margin when used at the recommended level.

Nuclear osteopontin-c is a prognostic breast cancer marker.

BACKGROUND: Although Osteopontin has been known as a marker for cancer progression, the elevated production of this cytokine is not specific for cancer. We have identified the splice variant Osteopontin-c as being absent from healthy tissue but associated with about 75% of breast cancer cases. However, in previous studies of Osteopontin-c, follow-up information was not available. METHODS: Here we have analysed 671 patients, comprising a cohort of 291 paraffin blocks plus a population-based case-control study of 380 arrayed breast tumor tissues. RESULTS: We find that high staining intensity of nuclear Osteopontin-c is strongly associated with mortality in patients with early breast cancer. Cytosolic staining for exon 4, reflective of Osteopontin-a and -b also predicts poor outcome. By contrast, total Osteopontin does not correlate with prognosis. These diverse assessments of Osteopontin also do not correlate with each other, suggesting distinct expression patterns for the variant forms. Consistent with its role in tumor progression, not tumor initiation, Osteopontin-c is not correlated with proliferation markers (Ki-67, cyclin A, cyclin B, cyclin E and cyclin D), neither is it correlated with ER, PR or HER2. CONCLUSIONS: The addition of Osteopontin-c immunohistochemistry to standard pathology work-ups may have prognostic benefit in early breast cancer diagnosis.

Risk factors for and impact of carbapenem-resistant Acinetobacter baumannii colonization and infection: matched case-control study.

The objective of this investigation was to identify risk factors for carbapenem-resistant Acinetobacter baumannii (CRAB) and its association with mortality. A population-based matched case-control study using the computerized database of Clalit Health Services (CHS) in the period between 2007 and 2012 was conducted. Hospitalized patients with CRAB colonization or infection were compared to hospitalized patients without evidence of A. baumannii, matched by age, ward of hospitalization, season, Charlson score, and length of hospitalization. Risk factors for CRAB isolation were searched for using multivariate analysis. Association of CRAB and other risk factors with mortality were assessed in the cohort. A total of 1190 patients with CRAB were matched to 1190 patients without CRAB. Low socioeconomic status was independently associated with CRAB isolation and CRAB bacteremia [odds ratio 2.18, 95% confidence interval (CI) 1.02-5]. Other risk factors were invasive procedures and bacteremia with other pathogens prior to CRAB isolation, and various comorbidities. Among all patients, CRAB isolation was independently associated with increased mortality (hazard ratio 2.33, 95% CI 2.08-2.6). Socioeconomic status is associated with health outcomes. Our population-based study revealed an almost doubled risk for CRAB in patients at lower socioeconomic status and an association with healthcare exposure. CRAB was associated with mortality and might become a risk indicator for complex morbidity and mortality.

Characterization of adsorbed water in MIL-53(Al) by FTIR spectroscopy and ab-initio calculations.

Here, we report ab-initio calculations developed with a twofold purpose: understand how adsorbed water molecules alter the infrared spectrum of the metal-organic framework MIL-53(Al) and to investigate which are the associated physico-chemical processes. The analyzed structures are the two anhydrous narrow (np⊘) and large (lp⊘) pore forms and the hydrated narrow pore form (np-H2O) of the MIL-53(Al). For these structures, we determined their corresponding infrared spectra (FTIR) and we identified the vibrational modes associated to the dominant spectral lines. We show that wagging and scissoring modes of CO2 give flexibility to the structure for facilitating the lp⊘- np⊘ transition. In our studies, this transition is identified by eight vibrational modes including the δCH(18a) vibrational mode currently used to identify the mentioned transition. We report an exhaustive band identification of the infrared spectra associated to the analyzed structures. Moreover, the FTIR for the np-H2O structure allowed us to identify four types of water molecules linked to the host structure by one to three hydrogen bonds.

Heterogeneous phenotype in children affected by non-autoimmune hypothyroidism: an update.

BACKGROUND: In the last decades, a higher incidence of congenital hypothyroidism (CH) has been recorded in Italy (1:1940) and worldwide, mainly due to the shift to lower screening TSH cutoffs. Although CH can also be caused by dysgenetic defects, most CH cases have recently been found to be more frequently associated with functional defects of an in situ thyroid gland. Although the clinical phenotype is milder with high prevalence of transient forms, some cases eventually prove to be permanent. RESULTS: Possible explanations of the raised incidence of CH are ethnic modifications of the screened population and the increasing incidence of preterm birth and multiple pregnancies. These findings are important in terms of public health and standardization of screening programmes for special at-risk categories such as preterms, acutely ill term neonates, low birth weight and very low birth weight infants, and newborns with specific drug exposure. Other environmental factors have contributed to the increased incidence of hypothyroidism, including thyroid disrupting chemicals, iodine supply (excess/deficiency), and drugs interfering with thyroid function. Finally, an increased prevalence of hypothyroidism has been documented in obese children and patients with syndromic forms (Williams, Down, Turner, pseudohypoparathyroidism). The clinical and molecular phenotype of patients with CH will be better defined thanks to novel genetic approach based on the systematic analysis of a panel of genes (TSHR, DUOX2, DUOXA, TPO, PDS, TG, NKX2.1, JAG1, GLIS3, FOXE1, PAX-8). CONCLUSIONS: This review summarizes significant advances in the epidemiology and aetiology of non-autoimmune hypothyroidism, with a focus on thyroid dysfunction in preterm infants.

Micro-CT analyses of historical bone samples presenting with osteomyelitis.

OBJECTIVE: Osteomyelitis is an inflammation of the bone marrow mainly caused by bacteria such as Staphylococcus aureus. It typically affects long bones, e.g. femora, tibiae and humeri. Recently micro-computed tomography (µCT) techniques offer the opportunity to investigate bone micro-architecture in great detail. Since there is no information on long bone microstructure in osteomyelitis, we studied historic bone samples with osteomyelitis by µCT. MATERIALS AND METHODS: We investigated 23 femora of 22 individuals suffering from osteomyelitis provided by the Collection of Anatomical Pathology, Museum of Natural History, Vienna (average age 44 ±19 years); 9 femora from body donors made available by the Department of Applied Anatomy, Medical University of Vienna (age range, 56-102 years) were studied as controls. Bone microstructure was assessed by µCT VISCOM X 8060 II with a minimal resolution of 18 µm. RESULTS: In the osteomyelitic femora, most prominent alterations were seen in the cortical compartment. In 71.4% of the individuals with osteomyelitis, cortical porosity occurred. 57.1% of the individuals showed cortical thinning. In 42.9% trabecularisation of cortical bone was observed. CONCLUSION: Osteomyelitis is associated with severe alterations of cortical bone structure otherwise typically observed at old age such as cortical porosity and cortical thinning.

Evaluating a health behaviour model for persons with and without an intellectual disability.

BACKGROUND: Based on the idea of the Common Sense Model of Illness Representations by Leventhal as well as Lohaus's concepts of health and illness, a health behaviour model was designed to explain health behaviours applied by persons with intellectual disabilities (ID). The key proposal of this model is that the way someone understands the concepts of health, illness and disability influences the way they perceive themselves and what behavioural approaches to them they take. METHOD: To test this model and explain health differences between the general population and person with ID, 230 people with ID and a comparative sample of 533 persons without ID were included in this Austrian study. Data were collected on general socio-demographics, personal perceptions of illness and disability, perceptions of oneself and health-related behaviours. RESULTS: Psychometric analysis of the instruments used showed that they were valid and reliable and hence can provide a valuable tool for studying health-related issues in persons with and without ID. With respect to the testing of the suggested health model, two latent variables were defined in accordance to the theory. The general model fit was evaluated by calculating different absolute and descriptive fit indices. Most indices indicated an acceptable model fit for all samples. CONCLUSIONS: This study presents the first attempt to explore the systematic differences in health behaviour between people with and without ID based on a suggested health model. Limitations of the study as well as implications for practice and future research are discussed.

[Drug safety: challenge in an aging society]. / Arzneimittelsicherheit : Herausforderung in einer alternden Gesellschaft.

BACKGROUND: Within the context of the demographic change the proportion of the elderly in the overall population is steadily increasing. At the same time elderly patients are prescribed a disproportionately high number of medicines in comparison to younger patients. In the light of multimorbidity and polypharmacy which affect a relevant portion of the older population, drug safety is of particular importance. RESULTS AND DISCUSSION: In recent years, the prescription of psychiatric drugs to elderly patients was repeatedly subjected to regulatory assessment and recommendations, for example the safety of antipsychotics in patients with dementia. As only limited information is often available with respect to the risks of medicines in the elderly population, additional efforts are necessary for improvement of the database. In this context, the system of spontaneous reporting, e.g. the reporting of cases of suspected adverse drug reactions to the responsible authorities, plays an important role with respect to the additional knowledge to be gathered. By reporting observed adverse drug reactions as well as by the quality of the reported information, physicians are able to significantly influence the effectiveness of this system in a positive way. OUTLOOK: As medical care for the majority of the elderly population is provided by general practitioners, adequate longitudinal studies are of special interest for investigating drug safety in the elderly. This aim is being pursued by the AgeCoDe study (German study on aging, cognition and dementia in primary care patients), a prospective, multicentre observational study, which is being carried out within the German competence network of degenerative dementia (Kompetenznetz Degenerative Demenzen).

Electron- and proton-impact excitation of hydrogenlike uranium in relativistic collisions.

The K shell excitation of H-like uranium (U(91+)) in relativistic collisions with different gaseous targets has been studied at the experimental storage ring at GSI Darmstadt. By performing measurements with different targets as well as with different collision energies, we were able to observe for the first time the effect of electron-impact excitation (EIE) process in the heaviest hydrogenlike ion. The large fine-structure splitting in H-like uranium allowed us to unambiguously resolve excitation into different L shell levels. State-of-the-art calculations performed within the relativistic framework which include excitation mechanisms due to both protons (nucleus) and electrons are in good agreement with the experimental findings. Moreover, our experimental data clearly demonstrate the importance of including the generalized Breit interaction in the treatment of the EIE process.

Interactions among pro-inflammatory cytokines, IGF system and thyroid function in pre-pubertal obese subjects.

Obesity is a state of chronic inflammation. Data on IGF system are often discrepant, and their relationships with mediators of inflammation are unknown. Furthermore, changes in thyroid function have been reported. We aimed at investigating the changes in these systems, and verify any relationships among cytokines, IGF system, thyroid function and insulin-insensitivity. Fifty obese pre-pubertal children, and 55 normal-weight subjects comparable for age and sex were enrolled. Serum IGF-I, IGF-II, IGFBP-1, IGFBP-2, IGFBP-3, IL-6 and TNF-alpha were assayed. In obese children insulin, TSH and FT4 were measured also, and the HOMA-IR index was calculated. Increased IGF-II, IL-6 and TNF-alpha, and decreased IGFBP-1 and IGFBP-2 concentrations were found in obese compared to normal-weight children. The IGF-I/IGFBP-3 molar ratio was also reduced in the obese subjects. In the obese children with high HOMA-IR index, IGFBP-1 and -2 serum concentrations were significantly decreased compared with those with normal insulin sensitivity, and in the obese subjects with increased TSH, IGFBP-2 concentrations were lower, and IGFBP-3 levels were higher compared to their counterparts with normal TSH levels. Among the significant correlations, BMISDS was correlated with IGF-II, and TSH. IGF-II concentrations showed a positive relationship with IL-6. TSH was correlated with IGFBP-2 also. The data showed interactions among IL-6, IGF system, insulin sensitivity, and thyroid function with changes being related to the degree of obesity. Chronic inflammation in obese children was confirmed. Some of the changes in the IGF system could be a consequence of insulin resistance and could account also for later complications in obese subjects.

Genetic defects of hydrogen peroxide generation in the thyroid gland.

Hydrogen peroxide (H2O2) is a key element in thyroid hormone biosynthesis. It is the substrate used by thyroid peroxidase for oxidation and incorporation of iodine into thyroglobulin, a process known as organification. The main enzymes composing the H2O2-generating system are the dual oxidase 2 (DUOX2) and the recently described DUOX maturation factor 2 (DUOXA2). Defects in these reactions lead to reduced thyroid hormone synthesis and hypothyroidism, with consequent increased TSH secretion and goiter. Since the first report in 2002 of DUOX2 mutations causing congenital hypothryoidism (CH), to date 25 different mutations have been described. Affected patients show a positive perchlorate discharge test and high phenotypic variability, ranging from transient to permanent forms of CH. Up to now, only two cases of CH due to DUOXA2 defects have been published. They also suggest the existence of a great genotype-phenotype variability. The phenotypic expression is probably influenced by genetic background and environmental factors. DUOX and DUOXA constitute a redundant system in which DUOX1/DUOXA1 can at least partially replace the function of DUOX2/DUOXA2. Furthermore, increased nutritional iodide could ensure a better use of H2O2 provided by DUOX1.