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The review of the literature summarizes and analyzes the material on inflammatory processes accompanying cardiovascular complications in diabetes mellitus. The role of endothelial dysfunction is shown leading to an increase in the permeability of the endothelium, accumulation of lipoproteins in the vessel wall, their modification, formation and secretion of cell adhesion molecules, which in turn leads to involvement of monocytes and their differentiation into inflammatory macrophages. The role of scavenger receptors in the deposition of cholesterol and the formation of foam cells was noted. The mechanisms of the inflammatory process initiation and the formation of inflammasоmes are considered in detail. The scheme of transduction of proinflammatory signals in the cell and participation of the key factor NF-κB integrating all incoming information and controlling the transactivation of genes involved in inflammation are described. It is shown that inflammation is key process in the development of vascular diseases in diabetes mellitus, and the suppression of these processes inhibits the progression of the disease reducing arterial damage and contributing to their healing.

Наведені історичні факти становлення медицини як науки з акцентом на розвиток ендокринології. В історичному плані з’ясована роль досліджень іноземних і вітчизняних учених та їхній внесок у розвиток хімії гормонів. З’ясована роль навчальних закладів, академій у формуванні світогляду майбутніх науковців, просуванні передового досвіду. Показано, як поступово накопичувалися знання з медицини: опис клінічних проявів, визначення лабораторних відмінностей. Можливість надання людині з ендокринним захворюванням патогенетично обґрунтованого лікування з’явилась у більшості випадків тільки після розвитку промислового синтезу гормональних препаратів. Праці багатьох учених відзначені Нобелівською премією за досягнення в галузі медицини та фізіології. Наведено визначення поняття «гормон», класифікацію, місця біосинтезу, особливості секреції, промисловий синтез деяких гормонів і сфери використання. Особлива увага приділяється опису нових методів синтезу тироксину, флутафарму та інших речовин.

The article describes the current understanding of the pathogenesis of different types of thyroid nodules. An algorithm for the diagnosis of thyroid diseases, which is aimed at verifying the morphological structure of goiter before the start of treatment, is presented in order to make the right decision on the indications for surgical treatment and its scope. The main methods for both conservative and surgical treatment of thyroid nodules are considered. The features of the treatment of pregnant women with thyroid nodules have been determined.

Background: A significant increase in the incidence of papillary thyroid carcinoma (PTC) in subjects exposed to radiation at a young age is a well-documented health consequence of the Chernobyl accident. The ongoing Thyroid Ultrasound Examination (TUE) program in children and adolescents of Fukushima Prefecture in Japan also indicated a high prevalence of PTC although its attribution to radiation exposure is a subject of debate. The objective of this study was to perform histopathological analysis of tumor architecture and invasive properties in (i) radiogenic post-Chernobyl and sporadic PTCs from Ukraine, and (ii) PTCs in patients from Fukushima and other Prefectures of Japan of comparable age groups. Methods: The Ukrainian radiogenic PTCs included 245 PTCs from patients who resided in three highly 131I-contaminated regions and 165 sporadic PTCs diagnosed in residents of the same regions who were born after the accident and therefore not exposed to radioiodine. The Japanese series included 115 PTCs detected during the preliminary and the first full-scale surveys of the TUE in Fukushima and 223 PTCs from patients resident in other Prefectures. All of the subjects were included in the main statistical analysis. Three additional analyses were performed limiting the subjects to children, adolescents, and adults. Results: Ukrainian radiogenic PTC was characterized by the higher frequency of tumors with a dominant solid-trabecular growth pattern and higher invasiveness, more frequent extrathyroidal extension, lymphatic/vascular invasion, regional and distant metastases when compared with sporadic Ukrainian PTC. The integrative "invasiveness score," based on five cancer characteristics, was also higher in the radiogenic group. The differences were most pronounced in children. In contrast, no significant differences in tumor morphology or invasiveness were observed between the two Japanese groups or the three age subgroups. The only statistically significant findings were the higher proportion of male patients, smaller mean tumor size, and higher frequency of T1b tumors in the Fukushima group. Conclusions: The difference in morphological features that indicate biological behavior of PTC between the radiation-related and sporadic groups from Ukraine, together with the lack of such in the two groups from Japan, strongly suggest a nonradiogenic etiology of PTC from Fukushima and other Prefectures.

Histopathological changes in the fusion oncogene-driven papillary thyroid carcinomas (PTCs) from children and adolescents exposed to Chernobyl fallout have been extensively studied. However, characteristics of the radiogenic BRAFV600E-positive PTCs, whose proportion is growing with time, are not well described yet. We analyzed the relationship between the BRAFV600E status (determined immunohistochemically with the VE1 antibody) and the clinicopathological features of 247 radiogenic and 138 sporadic PTCs from young Ukrainian patients aged ≤28 years. The frequency of BRAFV600E was increasing with patient age, consistently remaining lower in radiogenic PTCs. In both etiopathogenic groups, the BRAFV600E-positive PTCs more frequently had a dominant papillary growth pattern, smaller tumor size, higher Ki67 labeling index, and a frequency of the major indicators of tumor invasiveness that is lower than or equal to that of the BRAFV600E-negative tumors. Comparison of the BRAFV600E-positive PTCs across the groups found a virtual absence of differences. In contrast, the BRAFV600E-negative radiogenic PTCs displayed less frequent dominant papillary and more frequent solid growth patterns, lower Ki67 labeling index, and higher invasiveness than the BRAFV600E-negative sporadic tumors. Thus, BRAFV600E is not associated with a more aggressive course of PTC in young patients regardless of etiology. The major clinicopathological differences between the radiogenic and sporadic PTCs are observed among the BRAFV600E-negative tumors., Cancers, 13(23), art. no. 6038; 2021

An observational study was conducted in Ukraine to determine the independent mortality risks among adult inpatients with COVID-19. The results of treatment of COVID-19 inpatients ( n = 367) are presented, and waist circumference (WC) was measured. Logistic regression analysis was applied to evaluate the effects of factors on the risk of mortality. Odds ratios and 95% CIs for the association were calculated. One hundred and three of 367 subjects had fasting plasma glucose level that met the diabetes mellitus criteria (≥7.0 mmol/L), in 53 patients, diabetes mellitus was previously known. Two hundred and eleven patients did not have diabetes or hyperglycemia. Diabetes mellitus/hyperglycemia odds ratio 2.5 (CI 1.0–6.1), p = 0.045 loses statistical significance after standardization by age, waist circumference or fasting plasma glucose. No effect on gender, body mass index-determined obesity, or hypertension was found. The fasting plasma glucose (>8.5 mmol/L), age (≥61 years), and waist circumference (>105 cm) categories were associated with ORs 6.34 (CI 2.60–15.4); 4.12 (CI 1.37–12.4); 8.93 (CI 3.26–24.5), respectively. The optimal model of mortality risk with AUC 0.86 (CI 0.81–0.91) included the diabetes/heperglycemia and age categories as well as waist circumference as a continued variable. Waist circumference is an independent risk factor for mortality of inpatients with COVID-19.

Genomics of radiation-induced damage The potential adverse effects of exposures to radioactivity from nuclear accidents can include acute consequences such as radiation sickness, as well as long-term sequelae such as increased risk of cancer. There have been a few studies examining transgenerational risks of radiation exposure but the results have been inconclusive. Morton et al. analyzed papillary thyroid tumors, normal thyroid tissue, and blood from hundreds of survivors of the Chernobyl nuclear accident and compared them against those of unexposed patients. The findings offer insight into the process of radiation-induced carcinogenesis and characteristic patterns of DNA damage associated with environmental radiation exposure. In a separate study, Yeager et al. analyzed the genomes of 130 children and parents from families in which one or both parents had experienced gonadal radiation exposure related to the Chernobyl accident and the children were conceived between 1987 and 2002. Reassuringly, the authors did not find an increase in new germline mutations in this population. Science , this issue p. eabg2538 , p. 725

Thyroid ultrasound screening of young residents in Fukushima Prefecture, Japan, showed a high detection rate of papillary thyroid carcinoma (PTC). Detailed morphological analysis of these tumors was not presented to date. This study sets out to evaluate changes in histopathological and invasive characteristics of Fukushima PTC with time after the nuclear accident of March 2011 in all available cases and in different age subgroups. Histological specimens of 115 PTCs from patients aged 18 years or younger at the time of the Fukushima Dai‐ichi Nuclear Power Plant accident, who underwent surgical resection at Fukushima Medical University during 2012‐2016, were reviewed. Patients were divided into those treated during the first 4 years after the accident (n = 78, shorter‐onset) or later (n = 37, longer‐onset). The whole group and 3 age subgroups: children (aged less than 15 years), adolescents (aged from 15 to less than 19 years), and young adults (aged from 19 years) at surgery were analyzed. No statistically significant time‐related changes in tumor structure or invasiveness were found in the whole group or in age‐matched subgroups. Statistically significant age‐related downtrend was observed for intrathyroid spread in the whole group of patients. The absence of temporal changes in tumor morphological characteristics and tumor invasiveness strongly suggests common etiology of the shorter‐ and longer‐onset Fukushima PTCs, which are unlikely related to the effect of exposure to very low doses of radiation.

BACKGROUND: Children and adolescents exposed to radioactive iodine-131 (I-131) in fallout from the 1986 Chernobyl nuclear accident appear to be at increased risk of thyroid cancer and benign thyroid nodules. The prenatal period is also considered radiosensitive, and the fetal thyroid can absorb I-131 from the maternal circulation. OBJECTIVES: We aimed to estimate the risk of malignant and benign thyroid nodules in individuals exposed prenatally. METHODS: We studied a cohort of 2582 subjects in Ukraine with estimates of I-131 prenatal thyroid dose (mean = 72.6 mGy), who underwent two standardized thyroid screening examinations. To evaluate the dose-response relationship, we estimated the excess OR (EOR) using logistic regression. RESULTS: Based on a combined total of eight cases diagnosed at screenings from 2003 to 2006 and 2012 to 2015, we found a markedly elevated, albeit not statistically significant, dose-related risk of thyroid cancer (EOR/Gy = 3.91, 95% CI: –1.49, 65.66). At cycle 2 (n = 1,786), there was a strong and significant association between I-131 thyroid dose and screen-detected large benign nodules (≥10 mm) (EOR/Gy = 4.19, 95% CI: 0.68, 11.62; P = 0.009), but no significant increase in risk for small nodules (

To evaluate risk of thyroid neoplasia nearly 30 years following exposure to radioactive iodine (I-131) from the 1986 Chernobyl nuclear accident, we conducted a fifth cycle of thyroid screening of the Ukrainian-American cohort during 2012-2015, following four previous screening cycles started in 1998. We identified 47 thyroid cancers (TC) and 33 follicular adenomas (FA) among 10,073 individuals who were

The 1986 Chernobyl nuclear power plant accident increased papillary thyroid cancer (PTC) incidence in surrounding regions, particularly for 131I-exposed children. To investigate the contribution of environmental radiation to PTC characteristics and improve understanding of radiation-induced carcinogenesis, we analyzed genomic, transcriptomic, and epigenomic characteristics of 440 pathologically-confirmed fresh-frozen PTCs from Ukraine (359 with estimated childhood or in utero 131I exposure and 81 from unexposed children born after March 1987) and matched normal tissue (non-tumor thyroid tissue and/or blood). Mean age at PTC was 28.0 years (range: 10.0-45.6). Among 131I-exposed individuals, mean radiation dose was 250 mGy (range: 11.0-8,800). In multivariable models adjusted for age at PTC and sex, we observed radiation dose-dependent enrichment of fusion drivers (P=6.6 × 10−8), nearly all occurring in the MAPK pathway, as well as increases in small deletions (P=8.0 × 10−9) and simple/balanced structural variants (P=1.2 × 10−14). Further analyses demonstrated even stronger associations for those small deletions and simple/balanced structural variants that were clonal and bore hallmarks of non-homologous end-joining repair (deletions: P=4.9 × 10−31; simple/balanced structural variants: P=5.5 × 10−19). In contrast, radiation dose was not associated with subclonal small deletions (P=0.82) or subclonal simple/balanced structural variants (P=0.91). Additionally, radiation dose was not associated with TINS (locally templated insertions), which are characteristic of alt-end-joining repair (P=0.69). The effects of radiation on genomic alterations with more pronounced for those younger at exposure. Analyses generally were consistent with a linear radiation dose-response for all molecular characteristics except clonal small deletions. Analyses of transcriptomic and epigenomic features demonstrated strong associations with the PTC driver gene but not radiation dose. Our results point to DNA double-strand breaks as early carcinogenic events that subsequently enable PTC growth following environmental radiation exposure. Citation Format: Lindsay M. Morton, Danielle Karyadi, Chip Stewart, Tetiana Bogdanova, Eric Dawson, Mia Steinberg, Jieqiong Dai, Stephen Hartley, Sara Schonfeld, Joshua Sampson, Yosi Maruvka, Vidushi Kapoor, Dale Ramsden, Juan Carvajal-Garcia, Chuck Perou, Joel Parker, Marko Krznaric, Meredith Yeager, Joseph Boland, Amy Hutchinson, Belynda Hicks, Casey Dagnall, Julie Gastier-Foster, Jay Bowen, Olivia Lee, Mitchell Machiela, Elizabeth Cahoon, Alina Brenner, Kiyohiko Mabuchi, Vladimir Drozdovitch, Sergii Masiuk, Mykola Chepurny, Liudmyla Yu Zurnadzhy, Maureen Hatch, Amy Berrington de Gonzalez, Gerry Thomas, Mykola Tronko, Gad Getz, Stephen Chanock. Molecular characterization of papillary thyroid cancer in relation to ionizing radiation dose following the Chernobyl accident [abstract]. In: Proceedings of the AACR Virtual Special Conference on Radiation Science and Medicine; 2021 Mar 2-3. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(8_Suppl):Abstract nr PO-055.

This study set out to compare structural and invasive characteristics of sporadic papillary thyroid carcinoma (PTC) in age-matched groups of children and adolescents of Japan and Ukraine to provide detailed histopathological analysis of tumors from different geographical areas with different iodine intake. A total of 348 (160 Japanese and 188 Ukrainian) PTCs from patients without radiation history were analyzed initially as a combined pediatric group and then subdivided into childhood (aged ≤14 years) and adolescent (aged from 15 to ≤18 years) age series. On multivariate comparison, the Japanese pediatric PTC was characterized by a higher sex ratio (p=1.504E-4), and a higher frequency of microcarcinoma (p=0.039), papillary dominant growth pattern (p=0.024), focal oxyphilic cell metaplasia (p=7.644E-6), intrathyroid spread (p=0.010), lymphatic/vascular invasion (p=0.01) and regional lymph node metastases (p=3.540E-6). In the Ukrainian group, multifocal (p=0.004) and non-encapsulated tumors with the solid-trabecular growth pattern (p=0.05) were more frequent. Childhood Japanese PTCs differed from Ukrainian PTCs by more pronounced invasive properties such as lymphatic/vascular invasion and nodal disease, but did not differ by the dominant growth pattern. In adolescents, the differences were detected not only for lymph node metastases, but also for a higher frequency of the papillary dominant pattern in Japanese PTC. Overall, significantly higher frequencies of oxyphilic cell metaplasia and more pronounced invasive features observed in the Japanese PTC in both age-matched series represent the major differences between the tumors from two geographical areas.

This chapter analyzes histopathological characteristics of papillary thyroid carcinoma (PTC) in subjects of Ukraine who were children and adolescents at the time of the Chernobyl accident. Tumor architecture and invasive properties significantly changed with patients’ age at surgery increasing from 4 to 48 years and with the time elapsed after the accident extending to 30 years. Two major linear trends, the age- and time-related, were revealed for most pathological characteristics; some of them were ascending and some descending. “Radiogenic” PTC in subjects aged ≤4 years at the time of exposure who resided in three regions most contaminated by 131I differed from “sporadic” PTC in age-matched groups of patients from the same regions in terms of both tumor histoarchitectonics and invasiveness. “Radiogenic” PTC displayed a higher frequency of invasive features especially pronounced in children and adolescents. Changes in histopathological characteristics suggest that the phenotype of both “radiogenic” and “sporadic” PTCs becomes less invasive at older patients’ ages. The frequency of intermediate pathological diagnoses of thyroid tumors according to the WHO Classification of Tumours of Endocrine Organs, 4th edition, in the Ukrainian cases included in the Chernobyl Tissue Bank appeared to be not more than 3%.

AIM To compare the frequency of main histopathological characteristics, 131І thyroid radiation doses, invasive properties and post-operative follow-up of patients of different age groups with potentially radiogenic papillary thyroid carcinoma (PTC) with the presence and absence of oncocytic changes in tumor cells. MATERIALS AND METHODS PTC removed in 483 patients from high risk age-group for radiogenic thyroid cancer development (children and adolescents at the time of Chornobyl accident who lived in the northern regions of Ukraine: Kyiv, Zhytomyr, and Chernihiv regions) have been studied microscopically. RESULTS The frequency of PTC with the presence of oncocytic changes (OCh) in tumor cells increased significantly with increasing of patients' age at the time of surgery: from 8.3% in children 4-14 years old to 54.3% in adults 39-48 years old (ptrend < 0.0001). The presence of such changes is associated with papillary and solid-trabecular dominant tumor growth pattern in more than 90% of cases in each age group. The mean 131І thyroid dose in the whole series of PTC patients with OCh was significantly lower compared to the same index in PTC patients without OCh (493.7 mGy and 765.8 mGy, respectively, p < 0.0001). In addition, regional metastases recurrences were revealed more frequently in patients with OCh in primary PTC compared with patients without OCh in primary tumor (7.2% vs 1.5%, p = 0.0022). CONCLUSIONS Significantly increasing age-trend of OCh in PTC of patients affected by the Chornobyl fallout and operated at age from 4 to 48 years, as well as opposite decreasing linear age-trend of 131І thyroid dose may reflect a gradual increase of sporadic PTCs frequency in the potentially radiogenic series with time elapsed since accident. The frequency of oncocytic insensitive to radioiodine therapy of lymph node metastases recurrences also increased with patients age and OCh availability in primary PTC.

Materials and methods. Based on clinical and immunological studies, in this study, we present data on the establishment of mechanisms that are responsible for the development of early and late pre-clinical stages of the type 1 diabetes (T1D), obtained by studying diabetes-associated autoantibodies (DAAb) and the levels of basal and postprandial glycemia, and C-peptide secretion at the preclinical stage of T1D development in children and adolescents. Results. As a result we were able to form a group of marker-positive children with a genetic predisposition and an increased predicted risk of developing the diease. A total of 474 practically healthy normoglycemic children and adolescents aged 7 to 18 years were examined. An elevated titre of DAAb, mainly GADA and IA-2A was found in 94 (25.68 %) of 366 children with a genetic predisposition for at least of two determinants of DAAb, and the clinical onset of T1D manifesting in 68 (72.34 %) of them from 6 months to 15 years (30.9 ± 3.2 months). The formula of combined occurrence and values of simultaneously elevated titres of DAAb against islet autoantigens, namely, IA-2A + GADA, which is a predictor of the duration of the preclinical stage of T1D, was determined. Conclusions. It was established that the early preclinical development of T1D in DAAb + children was characterized by the presence of dysglycemia in the form of elevated glycemia 2 hours after the glucose tolerance test and a steady decrease in the secretion of stimulated C-peptide; additionally, dysglycemia was jointed as impaired fasting glycemia, and there was a decrease in both basal and stimulated secretions of C peptide, indicating the depletion of the potential of pancreatic beta-cells. Key words: type 1 diabetes (T1D), children and adolescents, diabetes-associated autoantibodies (DAAb), autoantibodies against glutamic acid decarboxylase (GADA), autoantibodies against tyrosine phosphatase (IA-2A), basal and postprandial glycemia, basal and stimulated C-peptide. For citation: Tronko MD, Mankovskyi BM, Popova VV, Zak KP. Concentration of diabetes-associated autoantibodies against islet autoantigens (IA-2A, GADA, IAA), levels of basal and postprandial glycemia, and secretory state of basal and stimulated C-peptide in the preclinical period of type 1 diabetes development in children and adolescents as immunological, metabolic and hormonal predictors of the clinical onset of the disease. Journal of the National Academy of Medical Sciences of Ukraine. 2019;25(3):285–95

International audience; [No abstract available]

Background: The issue of whether radiation-induced thyroid cancer is pathologically different from sporadic remains not fully answered. This study compared structural characteristics and invasive features of papillary thyroid carcinoma (PTC) in two age-matched groups: patients who were children (≤4 years old) at the time of the Chernobyl accident and who lived in three regions of Ukraine most contaminated by radioactive iodine (131)I (“radiogenic” cancer), and those who lived in the same regions but who were born after 1987 and were not exposed to (131)I (“sporadic” cancer). Further, the histopathologic features of PTC were analyzed in relation to age and individual (131)I thyroid dose. Methods: The study included 301 radiogenic and 194 sporadic PTCs. According to age at surgery, patients were subdivided into children (≤14 years old), adolescents (15–18 years old), and adults (19–28 years old). Statistical analyses included univariate tests and multivariable logistic regression within and across the age subgroups. Analyses of morphological features related to (131)I doses were conducted among exposed patients on categorical and continuous scales controlling for sex and age. Results: Among children, radiogenic PTC displayed a significantly higher frequency of tumors with a dominant solid growth pattern, intrathyroidal spread, extrathyroidal extension, lymphatic/vascular invasion, and distant metastases. Exposed adolescents more frequently displayed extrathyroidal extension, lymphatic/vascular invasion, and distant metastases. Exposed adults more frequently had intrathyroidal spread and extrathyroidal extension. The frequency of PTC with dominant papillary pattern and oxyphilic cell metaplasia was significantly lower in radiogenic compared to sporadic tumors for all age groups. Manifestations of tumor aggressiveness were most frequent in children compared to adolescents and adults regardless of etiology. Conclusions: Radiogenic PTC is less likely to demonstrate a dominant papillary growth pattern and more likely to display more aggressive tumor behavior than sporadic PTC. Histopathologic tumor aggressiveness declines with patient age in both radiogenic and sporadic cases.

Summary This study showed a clear dose-response relationship for the CLIP2 radiation marker in post-Chernobyl papillary thyroid carcinoma cohorts for young patients and hints to different molecular mechanisms in tumors induced at low doses compared to moderate/high doses., A previous study on papillary thyroid carcinomas (PTC) in young patients who were exposed to 131iodine from the Chernobyl fallout revealed an exclusive gain of chromosomal band 7q11.23 in exposed cases compared to an age-matched control cohort. CLIP2, a gene located within band 7q11.23 was shown to be differentially expressed between exposed and non-exposed cases at messenger RNA and protein level. Therefore, a standardized procedure for CLIP2 typing of PTCs has been developed in a follow-up study. Here we used CLIP2 typing data on 117 post-Chernobyl PTCs from two cohorts of exposed patients with individual dose estimates and 24 non-exposed controls to investigate a possible quantitative dose-response relationship of the CLIP2 marker. The ‘Genrisk-T’ cohort consisted of 45 PTCs and the ‘UkrAm’ cohort of 72 PTCs. Both cohorts differed in mean dose (0.59 Gy Genrisk-T, 1.2 Gy UkrAm) and mean age at exposure (AaE) (2 years Genrisk-T, 8 years UkrAm), whilst the median latency (16 years Genrisk-T, 18 years UkrAm) was comparable. We analyzed the association between the binary CLIP2 typing and continuous thyroid dose with logistic regression. A clear positive dose-response relationship was found for young PTC cases [age at operation (AaO) < 20 years, AaE < 5 years]. In the elder age group a higher proportion of sporadic tumors is assumed due to a negligible dose response, suggesting different molecular mechanisms in sporadic and radiation-induced cases. This is further supported by the association of elder patients (AaO > 20 years) with positivity for BRAF V600E mutation.

BackgroundSerum thyroglobulin (Tg) is associated with the presence of thyroid disease and has been proposed as a biomarker of iodine status. Few studies have examined factors related to serum Tg in populations environmentally exposed to ionizing radiation and living in regions with endemic mild-to-moderate iodine deficiency.MethodsWe screened 10,430 individuals who were living in Ukraine and under 18 years of age at the time of the 1986 Chernobyl Nuclear Power Plant accident for thyroid disease from 2001 to 2003. We estimated the percent change (PC) in serum Tg associated with demographic factors, iodine-131 thyroid dose, and indicators of thyroid structure and function using linear regression. We also examined these relationships for individuals with and without indications of thyroid abnormality.ResultsMean and median serum Tg levels were higher among participants with abnormal thyroid structure/function. Percent change in serum Tg increased among females, smokers and with older age (p-values

Iodine 131 (I-131), the principal component of nuclear fallout from the Chernobyl accident, concentrates in the thyroid gland and may pose risks to fetal development. To evaluate this, neonatal outcomes following the accident in April of 1986 were investigated in a cohort of 2582 in utero-exposed individuals from northern Ukraine for whom estimates of fetal thyroid I-131 dose were available. We carried out a retrospective review of cohort members’ prenatal, delivery and newborn records. The relationships of dose with neonatal anthropometrics and gestational length were modeled via linear regression with adjustment for potentially confounding variables. We found similar, statistically significant dose-dependent reductions in both head circumference (−1.0 cm/Gy, P = 0.005) and chest circumference (−0.9 cm/Gy, P = 0.023), as well as a similar but non-significant reduction in neonatal length (−0.6 cm/Gy, P = 0.169). Gestational length was significantly increased with increasing fetal dose (0.5 wks/Gy, P = 0.007). There was no significant (P > 0.1) effect of fetal dose on birth weight. The observed associations of radioiodine exposure with decreased head and chest circumference are consistent with those observed in the Japanese in utero-exposed atomic bomb survivors.

Background Exposure to ionizing radiation during childhood is a well-established risk factor for thyroid cancer. However, the genetic mechanisms of radiation-associated carcinogenesis remain not fully understood. Methods In this study, we used targeted next-generation sequencing and RNA-Seq to study 65 papillary thyroid cancers (PTCs) from patients in the Ukrainian-American cohort with measurement-based iodine-131 (I-131) thyroid doses received as a result of the Chernobyl accident. We fitted linear regression models to evaluate differences in distribution of risk factors for PTC according to type of genetic alteration and logistic regression models to evaluate the I-131 dose response. All statistical tests were two-sided. Results Driver mutations were identified in 96.9% of these thyroid cancers, including point mutations in 26.2% and gene fusions in 70.8% of cases. Novel driver fusions such as POR-BRAF, as well as STRN-ALK fusions that have not been implicated in radiation-associated cancer before, were found. The mean I-131 dose in cases with point mutations was 0.2 Gy (range = 0.013-1.05 Gy), statistically significantly lower than 1.4 Gy (range = 0.009-6.15 Gy) for cases with fusions (P < .001). No driver point mutations were found in tumors from individuals who received more than 1.1 Gy of radiation. Relative to tumors with point mutations, the proportion of tumors with gene fusions increased with radiation dose, reaching 87.8% among individuals exposed to 0.3 Gy or higher. With a limited study sample size, the estimated odds ratio at 1 Gy was 20.01 (95% confidence interval = 2.57 to 653.02, P < .001). In addition, after controlling for I-131 dose, we found higher odds ratios for gene fusion-positive PTCs associated with several specific demographic and geographic features. Conclusions Our data provide support for a link between I-131 thyroid dose and generation of carcinogenic gene fusions, the predominant mechanism of thyroid cancer associated with radiation exposure from the Chernobyl accident.

Geographic differences have been reported to affect the morphological and molecular features of papillary thyroid carcinomas (PTCs). The area around Chernobyl is well-known to be iodine-deficient in contrast to Japan, an iodine-rich country. We reviewed histological differences in adult PTC between Ukraine and Japan. In total, 112 PTCs from age- and sex-matched adults (Ukraine 56, Japan 56) were evaluated histologically for several factors including tumor size, capsulation, tumor components (papillary, follicular, solid, trabecular), lymph node metastasis, extrathyroid invasion, lymphocytic infiltration, oxyphilic metaplasia, and MIB-1 index. We demonstrated that tumors were smaller (1.56 vs. 2.13 cm, p

Background Our previous analysis of papillary thyroid carcinomas (PTC) from the Ukrainian-American cohort exposed to 131I from the Chernobyl accident found RET/PTC rearrangements and other driver mutations in 60% of tumors.

BACKGROUND: Childhood exposure to iodine-131 from the 1986 nuclear accident in Chernobyl, Ukraine, led to a sharp increase in papillary thyroid carcinoma (PTC) incidence in regions surrounding the reactor. Data concerning the association between genetic mutations in PTCs and individual radiation doses are limited. METHODS: Mutational analysis was performed on 62 PTCs diagnosed in a Ukrainian cohort of patients who were < 18 years old in 1986 and received 0.008 to 8.6 Gy of 131I to the thyroid. Associations between mutation types and 131I dose and other characteristics were explored. RESULTS: RET/PTC (ret proto-oncogene/papillary thyroid carcinoma) rearrangements were most common (35%), followed by BRAF (15%) and RAS (8%) point mutations. Two tumors carrying PAX8/PPARγ (paired box 8/peroxisome proliferator-activated receptor gamma) rearrangement were identified. A significant negative association with 131I dose for BRAF and RAS point mutations and a significant concave association with 131I dose, with an inflection point at 1.6 Gy and odds ratio of 2.1, based on a linear-quadratic model for RET/PTC and PAX8/PPARγ rearrangements were found. The trends with dose were significantly different between tumors with point mutations and rearrangements. Compared with point mutations, rearrangements were associated with residence in the relatively iodine-deficient Zhytomyr region, younger age at exposure or surgery, and male sex. CONCLUSIONS: These results provide the first demonstration of PAX8/PPARγ rearrangements in post-Chernobyl tumors and show different associations for point mutations and chromosomal rearrangements with 131I dose and other factors. These data support the relationship between chromosomal rearrangements, but not point mutations, and 131I exposure and point to a possible role of iodine deficiency in generation of RET/PTC rearrangements in these patients. Cancer 2013. © 2013 American Cancer Society.

The Ukrainian–American (UkrAm) thyroid study is a cohort study of thyroid cancer and other thyroid pathologies in Ukrainian individuals exposed as children or adolescents to radioactive fallout from the Chernobyl accident. The 13,243 cohort members with direct thyroid radioactivity measurements taken in May–June 1986 were first screened in 1998–2000. During the period 2001–07, three additional biennial cycles of thyroid screening examinations were carried out. A fifth screening was conducted between 2012 and 2015, with 76.4% of the original cohort coming for examinations. As a result of this latest screening, 47 new pathologically confirmed thyroid cancers were diagnosed by the end of 2015. Preliminary analyses of the fifth cycle data show a statistically significant excess of radiation-related thyroid cancer 26–30 years after I-131 exposure. Further follow-up of the UkrAm cohort would help clarify the dose dependence and long-term temporal pattern of risk. In addition, pooling of data from the UkrAm and parallel Belarusian cohort (BelAm) could improve the precision of risk assessment of thyroid disease after exposure at young ages to I-131 in Chernobyl fallout.

The incidence and pathological characteristics of thyroid cancer in subjects from Ukraine who were children and adolescents at the time of the Chernobyl accident, but reached adulthood at the time of surgery, were analyzed. A significant increase in thyroid cancer incidence in this age group persists up to 2014, and the incidence rate in the six most contaminated regions by 131I exceeded that in 21 less contaminated regions. Pathological analysis of 2634 thyroid carcinomas of the adults aged from 19 to 46 years at the time of surgery showed that papillary thyroid carcinoma (PTC) was the most prevalent type of thyroid cancer in all studied periods. With increasing time after the accident, PTCs with dominant papillary growth pattern have more pronounced invasive properties, but generally the tumors clearly become less aggressive, which is important and favorable for the postoperative prognosis.

For the purpose of improving retrospective internal thyroid dose estimations for children and adolescents following the Chernobyl accident, age- and gender-dependent thyroid masses have been estimated for the children of Kiev and Zhytomyr oblasts, which are two of the most contaminated regions of Northern Ukraine. For children ages 6-16 y, the thyroid masses were based on the measurements by ultrasound of the thyroid volumes of about 60,000 children performed by the Sasakawa Memorial Health Foundation in the 1990s. For children aged 0 to 36 mo, because thyroid mass values for Ukrainian children were not found in the literature, autopsies were performed for the specific purpose of this paper. Thyroid mass values for children aged 3-5 and 17-18 y were either interpolated or extrapolated from the measured data sets. The results for children aged 6-16 y indicate that the thyroid masses of rural children are, on average, slightly higher (by about 8%) than the thyroid masses of urban children. The geometric means of the thyroid masses were estimated as 5.2 g, 9.0 g, and 15.8 g for boys and 5.2 g, 9.4 g, and 16.0 g for girls aged 5, 10, and 15 y, respectively. Those values are greater than the reference values that ICRP recommends for iodine-sufficient populations, thus reflecting the fact that the northern part of Ukraine is iodine-deficient.

Microencapsulated human parathyroid tissue preserves the viability and high ability to secrete parathormone in the remote terms after transplantation to rats with experimen- tal hypoparathyroidism, which suggests good prospects for using this tissue in the presence of compensated hypofunctional state of para thyroid system in clinical practice. One of the most pending problems of the modern transplantology remains the search for the methods against rejection reaction and for prolongation of alo- and xenotrans- plant life in the recipient's organism wi thout a need for immunosuppressive therapy. Application of the latter for the long period can lead to such to such serious conse- quences as increase in the rate of infectious diseases and malignant tumors. The possible negative consequences of donor material transplantation could be prevented by means of encapsulation of the tiss ue or the cells into the capsules with bio- compatitive semipermeable membranes. While k eeping a possibility of free diffusion for small nutrition substances, hormo nes, messengers and metabolites they make a physical barrier for recipient's immune system and di sable infiltration of lymphocytes, leukocytes and macromolecules of imm unoglobulines and complement. 15 For the long time specialists did investig ate the three main approaches to encap- sulation of the transplantation biomaterial: intravascular macrocapsules, which have anastomoses with the vascular system on the principle of arterio-venous bypass; ex- travascular macrocapsules; mi crocapsules (the latter two methods stipulate for trans- plantation into different extravascular places). 15 Pros and contras of these three ap- proaches are being widely discussed and comp ared in the light of the possible usage under endocrine gland transplantation. Toda y all the three systems have shown a good results in the preclinical studies, but not a ll of them are sufficient for technical and

Relatively few data are available on the prevalence of hyperthyroidism (TSH concentrations of0.3 mIU/liter, with normal or elevated concentrations of free T4) in individuals exposed to radioiodines at low levels. The accident at the Chornobyl (Chernobyl) nuclear plant in Ukraine on April 26, 1986 exposed large numbers of residents to radioactive fallout, principally to iodine-131 ((131)I) (mean and median doses = 0.6 Gy and 0.2 Gy). We investigated the relationship between (131)I and prevalent hyperthyroidism among 11,853 individuals exposed as children or adolescents in Ukraine who underwent an in-depth, standardized thyroid gland screening examination 12-14 years later. Radioactivity measurements taken shortly after the accident were available for all subjects and were used to estimate individual thyroid doses. We identified 76 cases of hyperthyroidism (11 overt, 65 subclinical). Using logistic regression, we tested a variety of continuous risk models and conducted categorical analyses for all subjects combined and for females (53 cases, n = 5,767) and males (23 cases, n = 6,086) separately but found no convincing evidence of a dose-response relationship between (131)I and hyperthyroidism. There was some suggestion of elevated risk among females in an analysis based on a dichotomous dose model with a threshold of 0.5 Gy chosen empirically (OR = 1.86, P = 0.06), but the statistical significance level was reduced (P = 0.13) in a formal analysis with an estimated threshold. In summary, after a thorough exploration of the data, we found no statistically significant dose-response relationship between individual (131)I thyroid doses and prevalent hyperthyroidism.

Imperfect detection on screening tests can lead to erroneous conclusions about the natural history of thyroid nodules following radiation exposure. Our objective was to assess in a repeatedly screened I-131-exposed population the frequency with which a thyroid nodule could be retrospectively identified on ultrasonography studies preceding the one on which it was initially detected.A cohort of over 13,000 young people exposed to fallout from Chornobyl underwent ultrasonography screening at 2-year intervals from 1998 to 2007. The study group consisted of screening examinations on which a thyroid nodule was detected following one or more prior negative examinations. In the study group there were 48 cancers and 92 benign nodules. For each of these 140 index studies a comparison set was created containing all available prior studies plus (to test for bias) negative studies from control subjects. While viewing the index study, three independent reviewers scored the comparison studies for the presence and size of a preexisting nodule. Detection rates were compared for true priors versus controls, for cancer versus benign, and for histologic subtypes of papillary carcinoma.A preexisting nodule was identified by at least one reviewer in 24.0% of the true prior versus 8.3% of the controls and by all three reviewers in 11% versus 1% (Fisher's exact test, p 0.0001). There was no significant difference in detection rates between cancers and benign nodules (22.4% vs. 24.7%, p = 0.411). There was no correlation between time from prior to index study and change in nodule size for either malignant or benign nodules (r = 0.01, NS). There were no differences in detection rates or size among papillary cancer subtypes. Reviewers could not distinguish between true priors and controls.These findings, showing significant rates of undetected benign and malignant nodules and no evidence for rapid growth, suggest that conclusions drawn from screening studies about the frequency of late-developing, rapidly growing thyroid nodules following radiation exposure should be interpreted with caution.

In this study, we compared the rate of insulin requirement among adults with type 1 diabetes (T1D) in 24 Ukrainian regions. The glutamic acid decaroxylase 65 antibody (GADA), insulin antibody (IA), and plasma c-peptide levels were investigated. The data included the prevalent cases of T1D in Ukraine at the end of 2006. Only persons aged over 14 years at the time of inclusion into the Ukrainian register and diagnosed with diabetes before 30 years of age were included in this study (n=26796). A total of 86 T1D patients (42 males; 44 females) with a mean age of 27.5 years (0.86) and a mean diabetes duration of 10.3 (0.72) years (SE), were randomly selected from four regional diabetes registers. The GADA, IA, and the plasma c-peptide levels were also determined. The logistic regression model was used, and the odds ratio (OR) and 95% confidence interval (CI) were calculated. Furthermore, the differences in the T1D prevalence among the 24 Ukrainian regions were obtained (p0.001). In the "minimal" regional cluster (MIC), the prevalence rate was 6 (5-6), and in the "maximal" (MAC) regional cluster, it was -9 (8-9) per 10000 adults. For patients with a disease duration (DD) of up to 15 years (n=13677), the daily insulin dose (DID) was observed to increase linearly with DD (R=0.899, p0.001). The median insulin doses were standardized according to DD, and the values were lowest in the MIC and highest in the MAC populations: 45.89 (45.28-47.19) and 56.59 (53.33-57.88) U/24 h, respectively (p0.01). Furthermore, the level of HbA1c in the MAC of T1D patients was observed to be higher than that in the MIC (9.52+/-2.24%, n=240, and 8.57+/-3.29%, n=111, respectively; p0.01). In addition, the GADA levels and persistence in the MAC patients (n=38) were higher than that in the MIC patients (n=48): 14.1+/-4.6 and 3.2+/-1.2 U/ml, respectively, mean+/-SE; p=0.028; OR=9.66 (3.31-28.17), p0.001. Adjusting for age, gender, and duration of diabetes affected the results only slightly. Furthermore, the IA and c-peptide levels and their persistence were not observed to be associated with TD1 prevalence.

The Ukrainian American Cohort Study was established to evaluate the risk of thyroid disorders in a group exposed as children and adolescents to 131I by the Chernobyl accident (arithmetic mean thyroid dose, 0.79 grays). Individuals are screened by palpation and ultrasound and are referred to surgery according to fine-needle aspiration biopsy (FNA). However, the accuracy of FNA cytology for detecting histopathologically confirmed malignancy after this level of internal exposure to radioiodines is unknown.During the first screening cycle (1998-2000), 13,243 individuals were examined, 356 individuals with thyroid nodules were referred for FNA, 288 individuals completed the procedure, 85 individuals were referred to surgery, 82 individuals underwent surgery, and preoperative cytology was available for review in 78 individuals. Cytologic interpretation for the nodule that resulted in surgical referral was correlated with final pathomorphology; discrepancies were reviewed retrospectively; and the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of FNA cytology were calculated.All 24 cytologic interpretations that were definite for papillary thyroid cancer (PTC) were confirmed histopathologically (PPV, 100%); and, of 11 cytologic interpretations that were suspicious for PTC, 10 were confirmed (PPV, 90.9%). Ten of 41 FNAs that were interpreted as either definite or suspect for follicular neoplasm were confirmed as malignant (PPV, 24.4%), including 2 follicular thyroid cancers and 8 PTCs (all but 1 of the follicular or mixed subtypes). Depending on whether a cytologic interpretation of follicular neoplasm was considered "positive" or "negative," the sensitivity was 100% and 77.3%, respectively; similarly, the respective specificity was 17.6% and 97.1%, the respective PPV was 61.1% and 97.1%, and the respective NPV was 100% and 76.7%.Among children and adolescents who were exposed to 131I after the Chernobyl accident and were evaluated 12 to 14 years later, thyroid cytology had a sensitivity and a predictive value similar to those reported in unexposed populations.

The gender differences in stroke risk among diabetic patients with different treatments have not been studied previously. We aim to determine if there is a gender difference in nonfatal stroke risk in diabetic patients receiving different types of glucose-lowering treatments.In December 2005, data of type 2 diabetic patients were extracted from a nationwide population-based diabetes registry covering 11 Ukrainian regions. Male/female odds ratios (OR) for nonfatal stroke were calculated in three treatment groups: diet only 7,273/15,901, oral glucose-lowering drugs 15,109/33,913, and insulin 5,529/12,462 male/female. Male/female ORs of stroke were estimated using a logistic regression model.The age-adjusted ORs of stroke were higher among diabetic men compared with diabetic women with oral glucose-lowering drug treatment (OR 1.37, 95% CI 1.22-1.54) and diet treatment only (OR 1.53, 95% CI 1.35-1.73). No differences were found among patients who used insulin (OR 0.97, 95% CI 0.84-1.11). Further adjustment for duration of type 2 diabetes, body mass index (BMI), systolic blood pressure, total cholesterol, and smoking affected the results only slightly.The gender risks of nonfatal stroke in patients with type 2 diabetes appear to differ considerably depending on treatment types.

To compare the joint effects of different types of glucose-lowering treatment (oral drugs, insulin, and both) and duration of diabetes on total and cardiovascular mortality among diabetic patients.Study cohorts included 30,534 Ukrainian males and 58,909 females with type 2 diabetes. During the mean follow-up of 2.7 years, 7804 deaths were recorded.The multivariate-adjusted hazard ratios (HRs) for total mortality among diabetic patients, who used oral glucose-lowering drug (OGLD) only, insulin only, both insulin and OGLD, were 1.00, 2.34, and 2.22 in men, and 1.00, 2.12, and 2.20 in women, respectively. The multivariate-adjusted HRs for total mortality across categories of duration of diabetes (5, 5-9, 10-14, 15-19, and/=20 years) were 1.00, 1.17, 1.32, 1.43, and 1.57 (p(trend)0.001) in men, and 1.00, 1.13, 1.34, 1.74, and 1.68 (p(trend)0.001) in women, respectively. Diabetic patients who used insulin and reported longer duration of diabetes had the highest risk of total mortality.Type 2 diabetic patients treated with insulin show a greater risk of death than those treated with OGLD only. Increasing duration of diabetes is associated with an increased death risk. The combination of insulin treatment and longer duration of diabetes identifies a particular high death risk.

Pathology analysis of thyroid carcinomas removed in children and adolescents aged from 0 to 18 years at the time of the Chernobyl accident has been conducted in three age groups at the time of surgery (children aged up to 15, adolescents aged 15 to 18, and young adults aged 19 to 36 years) for three periods of observation: 1990–1995; 1996–2001; 2002–2004. In all age groups and for all periods of follow-up, papillary thyroid carcinomas (PTC) were predominant (> 90% of cases). A certain increase in the percentage of follicular carcinomas (FC) with increasing latency (time elapsed between surgery and Chernobyl accident) was noted. PTC were characterized by substantial changes in morphologic structure with increasing latency. The most aggressive PTC were reported in children operated on at the age of 4 to 14 years in 1990–1995 (shorter latency). With increasing latency an improvement of the character of biological behaviour of PTC was noted and confirmed by a decrease in the percentage of cases with extrathyroid spreading and presence of regional metastases. In patients born after the Chernobyl accident (1987 and later), as in children born before the accident, PTC were also prevalent, being characterized by marked invasive properties in cases of tumour size exceeding 1 cm. In addition, when compared with children born before the accident, a significantly higher percentage of FC was noted. Molecular-biology studies of PTC showed that RET rearrangements and BRAF mutations are closely related to tumour histological structure, latency, and patients' age at the time of surgery.

In the present paper are generalized data on the increase of thyroid cancer incidence in children and adolescents affected after the Chernobyl accident for the period 1986–2004. Beginning in 1990, a significant rise in the number of thyroid cancer cases and incidence was noted in the cohort aged 0–18 years at the time of the accident, especially among children aged 0–14 years. Patients' distribution by age at the time of the accident points out that the most significant increase in the number of thyroid cancer patients occurred at the expense of children who were aged up to 4 years in 1986. This is confirmed by the data concerning a steady increase just among children aged 0–4 years at the time of the accident, of additional thyroid cancer incidence with increasing thyroid exposure dose. The most pronounced increase has been reported for the highest average thyroid exposure dose of 1 Gy and more. The principles of early diagnosis of thyroid carcinoma lie in an objective assessment of oncological danger from all focal lesions of the thyroid, which were detected by ultrasound investigation. FNA of these tumors with cytology study of cell material allows improvement in the accuracy of preoperative diagnosis of thyroid cancer. The method of choice in the treatment of thyroid cancer is thyroidectomy followed by therapy with radioactive iodine and suppressive hormone therapy.

Background: There are limited data on the histopathology of papillary thyroid carcinomas (PTCs) diagnosed in irradiated populations. We evaluated the associations between iodine-131 dose and the histopathological characteristics of post-Chernobyl PTCs, the changes in these characteristics over time, and their associations with selected somatic mutations. Methods: This study included 115 PTCs diagnosed in a Ukrainian-American cohort (n=13 243) during prescreening and four successive thyroid screenings. Of these PTCs, 65 were subjected to somatic mutation profiling. All individuals were

Aims/hypothesis Numerous epidemiological studies have shown differences in seasonality of birth patterns between the general population and the group who develop type 1 diabetes mellitus. This finding indicates that environmental factors operating during pre- and/or postnatal development could be aetiologically important. We examined whether the pattern of month of birth for type 1 diabetes patients in Ukraine differs from that for total live births. Methods Data consist of prevalent cases of type 1 diabetes in Ukraine by the end of 2003. Cases are restricted to persons born after 1 January 1960, diagnosed with type 1 diabetes before the age of 30 years (n=20,117). People born during the same time in the general population (n=29,105,560) were the reference standard. Seasonal patterns were estimated using logistic regression with harmonic terms. Results We found a strongly significant seasonal pattern of type 1 diabetes incidence rates (p

BACKGROUND: The Ukrainian American Cohort Study was established to evaluate the risk of thyroid disorders in a group exposed as children and adolescents to 131I by the Chernobyl accident (arithmetic mean thyroid dose, 0.79 grays). Individuals are screened by palpation and ultrasound and are referred to surgery according to fine-needle aspiration biopsy (FNA). However, the accuracy of FNA cytology for detecting histopathologically confirmed malignancy after this level of internal exposure to radioiodines is unknown. METHODS: During the first screening cycle (1998-2000), 13,243 individuals were examined, 356 individuals with thyroid nodules were referred for FNA, 288 individuals completed the procedure, 85 individuals were referred to surgery, 82 individuals underwent surgery, and preoperative cytology was available for review in 78 individuals. Cytologic interpretation for the nodule that resulted in surgical referral was correlated with final pathomorphology; discrepancies were reviewed retrospectively; and the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of FNA cytology were calculated. RESULTS: All 24 cytologic interpretations that were definite for papillary thyroid cancer (PTC) were confirmed histopathologically (PPV, 100%); and, of 11 cytologic interpretations that were suspicious for PTC, 10 were confirmed (PPV, 90.9%). Ten of 41 FNAs that were interpreted as either definite or suspect for follicular neoplasm were confirmed as malignant (PPV, 24.4%), including 2 follicular thyroid cancers and 8 PTCs (all but 1 of the follicular or mixed subtypes). Depending on whether a cytologic interpretation of follicular neoplasm was considered “positive” or “negative,” the sensitivity was 100% and 77.3%, respectively; similarly, the respective specificity was 17.6% and 97.1%, the respective PPV was 61.1% and 97.1%, and the respective NPV was 100% and 76.7%. CONCLUSIONS: Among children and adolescents who were exposed to 131I after the Chernobyl accident and were evaluated 12 to 14 years later, thyroid cytology had a sensitivity and a predictive value similar to those reported in unexposed populations. Cancer (Cancer Cytopathol) 2009. Published 2009 by the American Cancer Society.

Urinary iodine concentrations were measured in 11,926 subjects who are participants in the Ukrainian-American Cohort Study of Thyroid Cancer and Other Thyroid Diseases Following the Chornobyl Accident. Measurements were made in two time periods corresponding to the first and second thyroid screening cycles (1998-2000, 2001-2003). These time periods fall before and after initiation of a government program to increase iodine sufficiency. Median urinary iodine concentrations did increase in the later time period compared to the earlier [47.5 microg/L, 95% confidence interval (CI) 46.5-48.9 microg/L versus 41.7 microg/L, 95% CI 40.4-42.5 microg/L], but levels remained in the mild-to-moderate iodine deficiency range as defined by the World Health Organization (WHO), indicating the need for further efforts at iodination. In both time periods, urinary iodine levels were found to vary by place of residence and were lower in rural compared to urban areas. Iodine status needs to be considered when evaluating risk of thyroid cancer and other thyroid diseases.

In this study, the frequency of BRAF mutation was investigated in a series of 67 cases of papillary thyroid cancer (PTC) in patients from Ukraine. Thirty-two patients were aged 30 years or older at the time of diagnosis and 35 were under 16. Tumour was microdissected from paraffin wax-embedded sections, DNA extracted, and the presence of the BRAF T1796A mutation demonstrated by two different methods: PCR followed by restriction enzyme digestion or primer extension assay and detection using MALDI-TOF mass spectrometry. Eighteen (58%) of the adult cases, but only one of the 35 cases aged less than 16 harboured a BRAF T1796A mutation. There was complete agreement between the two methods used, suggesting that the MALDI-TOF assay is a robust alternative to conventional mutation analysis. RET rearrangement was also examined in the young cohort. The overall frequency of RET rearrangement was 45.7%. Eight of the younger group of patients were born after 1 December 1986 and were therefore not exposed to radioiodine in fallout from Chernobyl. None of the PTCs from these eight patients were positive for BRAF mutation. The frequency of RET rearrangement was 44% in the 27 cases exposed to radiation and 50% in the eight not exposed. These results suggest that the different molecular biological profiles observed are associated with the age of the patient at diagnosis with PTC, rather than being associated with radiation exposure.

The thyroid gland in children is one of the organs that is most sensitive to external exposure to X and gamma rays. However, data on the risk of thyroid cancer in children after exposure to radioactive iodines are sparse. The Chornobyl accident in Ukraine in 1986 led to the exposure of large populations to radioactive iodines, particularly (131)I. This paper describes an ongoing cohort study being conducted in Belarus and Ukraine that includes 25,161 subjects under the age of 18 years in 1986 who are being screened for thyroid diseases every 2 years. Individual thyroid doses are being estimated for all study subjects based on measurement of the radioactivity of the thyroid gland made in 1986 together with a radioecological model and interview data. Approximately 100 histologically confirmed thyroid cancers were detected as a consequence of the first round of screening. The data will enable fitting appropriate dose-response models, which are important in both radiation epidemiology and public health for prediction of risks from exposure to radioactive iodines from medical sources and any future nuclear accidents. Plans are to continue to follow-up the cohort for at least three screening cycles, which will lead to more precise estimates of risk.

For the period 1998–2002, in the framework of the Ukraine–USA Thyroid Project, medical screening examinations have been conducted to subjects who were aged 0 to 18 years at the time of the Chernobyl accident. These were residents of eight districts, from Kyiv, Chernihiv, and Zhytomyr regions of the Ukraine, having been most affected following the Chernobyl accident, and having received within several weeks after the accident direct measurements of thyroid doses of gamma radiation. For the period 1998–2000, 13227 cohort subjects have undergone screening, and in 2001–2002, a repeat screening was performed. As a result of screening, 64 cases of thyroid carcinoma have been identified, including 43 cases after the first screening and 21 cases after the second screening. The distribution of patients by thyroid exposure dose pointed out a predominance of cancer cases in the high-dose group (exposure dose exceeding 1.0 Gy). In addition, 27 cases of benign surgical thyroid pathology have been identified at the first screening, among which were diagnosed 18 cases of follicular adenoma, two cases of multinodular adenomatous goiter, four cases of nodular solitary goiter, one case of fibrous nodule with degenerative changes, one case of diffuse toxic goiter (Graves' disease), and one case of diffuse euthyroid goiter.

The Chernobyl nuclear power plant accident in Ukraine in 1986 led to widespread radioactive releases into the environment - primarily of radioiodines and cesium - heavily affecting the northern portions of the country, with settlement-averaged thyroid doses estimated to range from 10 mGy to more than 10 Gy. The increased risk of thyroid cancer among exposed children and adolescents is well established but the impact of radioactive contamination on the risk of other types of cancer is much less certain. To provide data on a public health issue of major importance, we have analyzed the incidence of non-thyroid cancers during the post-Chernobyl period in a well-defined cohort of 13,203 individuals who were

Prenatal exposure to external radiation has been linked to growth retardation among atomic bomb survivors in adolescence. It is unclear from previous studies whether in utero exposure to internal radiation such as iodine-131 (I-131), which concentrates in the thyroid gland, has an effect on physical growth. We examined the associations between estimated thyroid gland dose from prenatal exposure to I-131 and self-reported height and weight in a cohort of 2,460 individuals exposed to radioactive fallout from the 1986 Chernobyl nuclear accident [mean I-131 dose = 72 (mGy)] and screened for thyroid diseases in adolescence. Using multivariable linear regression models, we estimated the mean differences in height, weight and body mass index (BMI) per unit increase in dose (100 mGy) in models adjusted for gender, age at examination, type of residence (rural/urban) and presence of thyroid disease diagnosed at screening. All of the adjustment factors as well as the trimester of exposure were evaluated as potential modifiers of the dose response. Overall, no significant dose response was found for height (P = 0.29), weight (P = 0.14) or BMI (P = 0.16). We found significant modification of the dose response for weight and BMI by presence/absence of thyroid disease (P = 0.02 and P = 0.03, respectively), but not for other factors. In individuals without thyroid disease (n = 1,856), there was a weak, significant association between I-131 thyroid dose and higher weight (210 g per 100 mGy, P = 0.02) or BMI (70 g/m2 per 100 mGy, P = 0.02) that depended on individuals (n = 52) exposed to ≥500 mGy. In individuals with thyroid disease (n = 579, 67.4% with simple diffuse goiter) no significant association with I-131 for weight (P = 0.14) or BMI (P = 0.14) was found. These results do not support the hypothesis that in utero exposure to I-131 at levels experienced by a majority of study subjects may be associated with meaningful differences in adolescent anthropometry. However, additional studies are needed to clarify whether in utero exposure to I-131 at levels > = 500 mGy may be associated with increases in weight/BMI and to evaluate the confounding or modifying role of thyroid disease, past iodine deficiency, maternal and prenatal/postnatal factors.

Keywords Birthcohorts.Early-lifeconditions.Month-of-birthpattern.Type2diabetesTo the Editor: Epidemiological studies have repeatedlyshown a link between poor fetal growth and increased riskof developing type 2 diabetes [1]. Month of birth is a goodinstrument for the assessment of effects of early growth onadult health independent of life-course factors. This is truebecause in decades past there were important seasonaldifferences in nutrition, especially in developing countriessuch as Ukraine. These differences in access to high-qualityfood supply can potentially influence intrauterine growth,depending on the month of gestation [2]. Other possibletriggering factors for developing type 2 diabetes, such asproduction of vitamin D [3] and outdoor temperature [4],also tend to change seasonally.Seasonal pattern of birth in type 1 diabetic children andadolescents was repeatedly described around the world,including our recent study in Ukraine [5]. In contrast, theseasonality of birth in type 2 diabetic patients waspreviously reported only in a few small-sample studies,e.g. in 155 African-American type 2 diabetic adolescent [6]and 282 adult patients in the Netherlands [7]. To studywhether abnormal seasonality of birth exists in middle- toold-aged type 2 diabetic patients in Ukraine, we comparedthe month-of-birth patterns in type 2 diabetic patients in threelarge Ukrainian regions with those in general populations.Information on date of birth, sex and year of diagnosiswas extracted from the nationwide primary-care-basedUkrainian diabetes mellitus register created in 2000 in theInstitute of Endocrinology, Kiev, Ukraine. The definition oftype 2 diabetes was based on onset after 39 years of age,irrespective of the type of treatment.Cases were identified from the three regional diabetesregisters with high completeness of ascertainment: Cherni-giv (100%), Kherson (99.7%) and Rivne (86.2%). Theseregisters cover 7.4% of the total Ukraine population. Afemale excess was evident in all three registers. Cases wereall people alive with diagnosis of type 2 diabetes as of1 January 2008, and who were diagnosed at age 40 or later.Only people born before 1 January 1960 were included;thus all cases included were at least 48. In total, 17,510male and 34,704 female type 2 diabetic patients werefinally included in the study. Reference populations werebased on the Ukraine census 2001 depersonalised data.These populations included people who had been bornduring the same period and were residents of the sameregions: Chernigiv, 247,253 men and 369,357 women;Kherson, 208,944 men and 291,802 women; Rivne,189,887 men and 260,674 women.