Thyroid volume is the key predictor of hyperthyroidism remission after radioactive iodine therapy in pediatric patients.

Graves' disease (GD) is the leading cause of hyperthyroidism in pediatric patients. Radioactive iodine therapy (RAIT) is widely used to treat GD. However, it is still unclear exactly what determines the efficacy of RAIT in childhood and adolescence. The objective of our study was to reveal the most significant predictors of the efficacy of RAIT in pediatric GD patients. A single-center prospective observational exploratory study enrolled 144 pediatric patients (124 females and 20 males) between 8 and 18 years of age who underwent dosimetry-guided RAIT for GD for the first time. The estimated parameters included sex, age, thyroid volume, thyroid stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone receptor antibodies (TRABs) at baseline and 12 months after RAIT, 10- to 20-min 99mTc thyroid uptake (%), maximum thyroid 131I uptake (%), specific 131I uptake (MBq/g), and therapeutic activity of 131I (MBq), which was limited to 1100 MBq. The Fisher's exact test, Mann-Whitney U-test, Wilcoxon signed-rank test, ROC analysis, and the Youden index were used for statistical analysis. Twelve months after RAIT, 119 patients (83%) successfully achieved remission, 6 patients (4%) had euthyroidism, and hyperthyroidism persisted in 19 patients (13%). Thyroid volume decreased from 17.6 [14.6; 24.1] to 9.3 [7.6; 13.3] mL 12 months after the treatment (p < 0.001). The main predictor that showed a statistically significant difference between the groups of patients who achieved and did not achieve remission of GD hyperthyroidism after RAIT was the initial thyroid volume. Using the Youden index, the optimal cut-off point for the initial thyroid volume at 45.4 mL was determined.     Conclusion: The dosimetry-guided RAIT in pediatric GD patients was 83% effective at 12 months after the treatment, and the initial thyroid volume of less than 45.4 mL was the most important predictor of RAIT success. Other predictors identified in our work included FT4 levels, TRABs levels, 99mTc-pertechnetate uptake, and specific 131I uptake. What is Known: •Radioiodine therapy is a common, effective, and safe treatment for pediatric patients with Graves' disease. What is New: •The initial thyroid volume in pediatric GD patients is an important predictor of achieving hypothyroidism following radioiodine therapy. If the thyroid volume is less than 45.4 ml, radioiodine therapy limited to 1100 MBq will be effective definitive treatment.

First Satellite Tagging of the Northern Fur Seals (Callorhinus ursinus) on the Tyuleniy Island, the Sea of Okhotsk.

In October 2018, three Northern fur seals (two adult females and one juvenile male) were deployed with satellite tags on the Tyuleniy Island in the Sea of Okhotsk. The operational time of the tags ranged from 33 to 203 days. The adult females started their winter migration in the first half of November; the initial stage of their winter migration occurred in the Japan/East Sea, which they entered through the La Perouse Strait. The juvenile male left the rookery in mid-October, crossed the Sea of Okhotsk in a north-western direction and returned to the south. The male had reached the coastal areas of Hokkaido Island, Japan by the end of November. From the Sea of Okhotsk, the male entered the Pacific Ocean through the Yekaterina Strait and subsequently entered the Japan/East Sea via the Tsugaru Strait. The winter foraging of the male occurred within the north-eastern part of the Japan/East Sea just off the Tsugaru Strait. After 3 months, the male returned to the Pacific and remained off the Sanriku Coast (Honshu Island).

Dependence of radioactive iodine-131 capture by the lacrimal ducts on the tear production level.

Purpose: Secondary acquired lacrimal duct obstruction (SALDO) is one of the complications of radioiodine therapy. SALDO is formed a few months after therapy if there is a sufficient uptake of radioactive iodine by the nasolacrimal duct. To date, risk factors leading to SALDO are unclear. The objective was to determine the correlation between the tear production level and radioactive iodine-131 uptake in the lacrimal ducts. Methods: Basal and reflex tear production was studied in 64 eyes prior to the therapy with radioactive iodine-131 after drug-induced hypothyroidism. The condition of the ocular surface was assessed using the Ocular Surface Disease Index (OSDI) questionnaire. Seventy-two hours after the radioactive iodine therapy, scintigraphy was performed, which determined the presence or absence of iodine-131 in the lacrimal ducts. T-statistics and the Mann-Whitney criterion were used to identify the differences between the groups. The differences were considered significant at P ≤ 0.05. The current tear production level in patients receiving radioiodine therapy was determined using a mathematical model. Results: A statistically significant difference between the basal (p = 0.044) and reflex (p = 0.015) tear production levels was found in cases with and without iodine-131 uptake by the lacrimal ducts. The probable current tear production level corresponds to the sum of basal and 10-20% of reflex tear production. The uptake of iodine-131 was found regardless of the OSDI results. Conclusion: The probability of iodine-131 uptake by the lacrimal ducts rises as the tear production level increases.

Entanglement of Steller sea lions (Eumetopias jubatus) in man-made marine debris on Tyuleniy Island, Sea of Okhotsk.

The present report provides data on entanglement of Steller sea lions (SSL) in marine debris on Tyuleniy Island, Sea of Okhotsk. The frequency of entanglement depending on the material, sex, and age of animals was estimated. A total of 133 SSL were recorded as having debris on their bodies, or an average of 22.2 individuals per year. The relative rate of entanglement over the observation years ranged from 1.48 to 1.97% of their total number. The entangled individuals were both males and females of all ages, but young males constituted the largest proportion among them (5.2%). The entangled SSL most frequently (43.2%) had neck collars (the material is not defined) and, less frequently, packaging bands (23.4%), nets (17.7%), and other debris. Most of marine litter found on SSL is associated with commercial fishing activities. On Tyuleniy Island, the rate of SSL entanglement is higher than in the eastern part of the species' range.

Correction: Migrations of young spotted seals (Phoca largha) from Peter the Great Bay, Sea of Japan/East Sea, and the pattern of their use of seasonal habitats.

[This corrects the article DOI: 10.1371/journal.pone.0244232.].

Analysis of essential and non-essential trace elements in the organs of a mother-fetus pair of spotted seals (Phoca largha) from the Sea of Japan.

Concentrations of 22 essential and non-essential trace elements (Be, Al, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Mo, Ag, Cd, Sb, Ba, Tl, Pb, Th, U, and Hg) were measured in the organs of a mother-fetus pair (at the last trimester of pregnancy) of spotted seals from the Sea of ​Japan. The concentrations of eleven elements are reported for the first time. Eight organs of the pair were examined: lungs, heart, liver, kidneys, intestines, spleen, muscles, and bones. All trace elements detected in the organs of the mother were found also in the organs of the fetus at various concentrations. Placenta is not an effective barrier to prevent non-essential elements from getting into the fetus, but can control entry of some of them, e.g., aluminum, cadmium, and mercury. In most organs of the fetus, the concentrations of toxic trace elements (beryllium, antimony, thorium, and uranium) were noticeably higher than in the same organs of the mother, which indicates that during pregnancy female removes excess of non-essential trace elements by transferring them to the fetal body through the placental barrier.

Migrations of young spotted seals (Phoca largha) from Peter the Great Bay, Sea of Japan/East Sea, and the pattern of their use of seasonal habitats.

We studied the migrations of young spotted seals during their annual cycle. In May 2017, we attached satellite tags (SPOT-293A) to three individuals (two underyearlings and one yearling) captured at their breeding ground in Peter the Great Bay, western Sea of Japan/East Sea. The operational time of the installed tags ranged from 207 to 333 days; a total of 27195 locations were uploaded. All three seals migrated east and further north along the coast of the mainland. The average daily migration speed of the seals ranged between 70 and 135 km/day. The yearling moved faster than the underyearlings. During early August, they arrived at their summer habitats, which were located in the northern part of the Tatar Strait (Sea of Japan/East Sea) for the underyearling seals and in Aniva Bay (Sea of Okhotsk) for the yearling seal. While moving from the place of tagging to the summer feeding grounds, the seals covered a distance of 2300 to 3100 km. From August to October, each seal permanently stayed within the same isolated area. The reverse migration of all three seals began in November. When the seals traveled south, they used the same routes by which they had moved north in the spring, but they moved at a faster speed. By December, two seals returned to their natal islands, where both stayed until their transmitters stopped sending signals (in March 2018).

[Radioiodine therapy outcome in toxic multinodular goiter patient with concomitant hereditary Hasharon hemoglobinopathy].

This research describes a clinical case of treatment of a patient with thyrotoxicosis with concomitant hematological pathology – carriage of unstable hemoglobin Hasharon. A patient diagnosed with «Diffuse toxic nodular goiter. Thyrotoxicosis of medium severity. Drug-induced hypothyroidism» was admitted to the Department of radionuclide therapy for the purpose of treatment with radioactive iodine. Onset of disease - summer 2018 (thyroid-stimulating hormone (TSH) – 0 mIU/ml). The instrumental studies (ultrasound, scintillation scanning of the thyroid gland) were performed at the pre-radioiodine therapy (RIT) diagnostic stage. The history of the disease indicates, that in 2000 the patient was suspected of having abnormal hemoglobin, since then no examinations have been conducted and anemia has never been detected. The diagnosis of ancestral hemoglobinopathy with the presence (17%) of unstable Hasharon-Sinai-Sealy hemoglobin in a heterozygous form was verified during the preparation to RIT. The radionuclide therapy I131 with activity of 400 MBq was performed on 02.07.2019. The monthly monitoring of laboratory and instrumental indicants was carried out during the post-therapeutic period: the state of hypothyroidism was reached by the end of 2 months after RT, no episodes of significant increase in bilirubin levels were observed during the observation period; no side effects from RT were stated. It becomes possible based on the example of the above observation, to judge the safety of conducting RT for treatment of thyrotoxicosis in patients with similar hemoglobinopathy, without excluding, however, the need for an individual approach in each case.

[Predictors of the efficacy of radioiodine therapy of Graves' disease in children and adolescents].

RATIONALE: Insufficient world-wide clinical experience in radioiodine therapy (RIT) for Graves' disease (GD) in children and adolescents, and limited knowledge of the predictors of RIT efficacy. AIMS: Analysis and identification of the most significant predictors of the efficacy of RIT in children and adolescents with Graves' disease. MATERIALS AND METHODS: A total of 55 patients (48 females and 7 males) aged from 8 to 18 years receiving primary RIT for GD were enrolled. RIT planning was based on the dosimetric method. Analyzed parameters included gender, age, ultrasound thyroid volume before and 6 months after treatment, the presence of endocrine ophthalmopathy, duration of antithyroid drug (ATD) therapy, relapse of thyrotoxicosis after ATD dose reduction, blood fT3, fT4 and TSH levels initially and at 1, 3, 6 months after treatment, TSH receptor Ab initially and at 3 and 6 months after treatment, thyroid 99mTc-pertechnetate uptake at 10-20 minutes (%), maximum thyroid 131I uptake (%), specific 131I uptake (MBq/g) and therapeutic 131I activity (MBq). Fisher exact test, non-parametric Mann-Whitney test, Wilcoxon signed-rank test, logistic regression modelling, ROC-analysis, proportional hazard model (the Cox regression), the Kaplan-Meier method and log-rank test were used for statistical analysis as appropriate. RESULTS: Six months after RIT, hypothyroidism was achieved in 45 (81.8%), euthyroid state - in 2 (3.6%), and in 8 (14.6%) patients thyrotoxicosis persisted. On univariate statistical analysis, the smaller thyroid volume, higher fT4 and lower TSH receptor Ab levels, lower 99mTc-pertechnetate uptake and higher specific 131I uptake were associated with hypothyroidism. On multivariate logistic regression analysis, the older patient's age (p=0.011), smaller thyroid volume (p=0.003) and higher fT4 (p=0.024) were independent predictors of RIT efficacy. Thyroid volume was also the only variable associated with achievement of hypothyroidism in time after RIT (p=0.011). CONCLUSION: The efficacy of dosimetry-based RIT in children and adolescents with GD 6 months after treatment was 81.2%. Older patients' age, smaller thyroid volume and higher fT4 level were independent predictors of therapy success. Smaller thyroid volume was also a predictor of the favorable time-related outcome. Statistical models obtained in this work may be used to prospectively estimate the chance of efficient RIT for GD in pediatric patients.

Organochlorine pesticides (HCH and DDT) in blubber of spotted seals (Phoca largha) from the western Sea of Japan.

In 2014-2019, a total of 31 blubber samples were collected from spotted seals (Phoca largha) in the western Sea of Japan. The samples were analyzed by gas chromatography to determine level of organochlorine pesticides (OCPs). The concentration of hexachlorocyclohexane and its isomers (∑HCH) ranged from 389 to 50,070 ng/g lipid weght; the concentration of dichlorodiphenyltrichloroethane and its metabolites (∑DDT), ranged from 62,720 to 1,110,930 ng/g lipid wt. Transfer of HCH and DDT from mother to pup during pregnancy and lactation was documented. The OCP concentration in blubber of spotted seals from the western Sea of Japan is one to two orders of magnitude higher than in spotted seals inhabiting waters off the Japan coast. Organochlorines detected in the western Sea of Japan likely come from some countries of Southeast Asia still using OCPs in the agriculture sector.

Entanglement of northern fur seals (Callorhinus ursinus) in marine debris on Tyuleniy Island (Sea of Okhotsk) in 1998-2013.

The systematic annual observations of the northern fur seal rookery on Tyuleniy (= Robben) Island, Sea of Okhotsk, were started in 1958. Since 1975, all seals entangled in marine debris have been registered. Some of the data on this issue, collected on the island in the late 20th century, were published earlier. This report provides data for the period of completion of the commercial sealing (from 1998 to 2013). During this period, a total of 867 fur seals were observed entangled in marine debris, including 212 bulls, 97 half-bulls, 223 bachelors, and 335 females. The estimated mean annual number of entangled fur seals in 1998-2013 is 1113 individuals. Marine debris was found mainly on the neck and, less frequently, on the head and front flippers of the animals. This included pieces of fishing nets, packaging bands, ropes, fishing lines, and other items of anthropogenic origin.

Hair mercury concentrations in the spotted seal (Phoca largha) pups from the Sea of Japan.

This publication presents the results of a study of the total mercury (THg) concentration in the fetal hair (lanugo) of the young spotted seals inhabiting the Peter the Great Bay, Sea of Japan. We analyzed samples from pups that were collected in 2014-2017 at the seal breeding grounds. The concentration of total mercury was determined by atomic absorption spectrometry. The concentration of THg ranged from 1.52 to 6.68 µg/g dry weight. Mercury concentration in the lanugo exceeds that found in the environment (bottom sediments, sea water) and in other animals inhabiting the Bay. At the same time, the level was generally lower than that found in young seals of most other pinniped species (Steller sea lion Eumetopias jubatus, Northern fur seal Callorhinus ursinus, Harbor seal Phoca vitulina richardsi, Northern elephant seal Mirounga angustirostris, California sea lion Zalophus californianus) from the North Pacific.

Mercury in organs of Pacific walruses (Odobenus rosmarus divergens) from the Bering Sea.

The Pacific walrus (Odobenus rosmarus divergens) is still used as an important source of protein-rich food by indigenous peoples of Chukotka, Alaska, and other Arctic regions. Total mercury (THg) concentration was measured in eight internal organs of walruses. Samples were taken from 22 individuals (11 males and 11 females). Age of the animals ranged from 1 to 30 years. All the walruses were harvested by local hunters from the coastal waters off the Chukchi Peninsula (Russia) during the autumn of 2011. Total mercury concentration in the samples was determined by atomic absorption method. No statistically significant difference in the level of mercury was found between males and females. Mercury was detected in all the organs of the studied walruses. The highest total mercury concentration was recorded from excretory organs: liver and kidneys. The level of mercury in liver (mean = 1.87 µg/g, range = 0.05-5.87) was by an order of magnitude higher than in kidneys (mean = 0.54 µg/g, range = 0.09-1.64.); in kidneys, it was by an order of magnitude higher than in the rest of the organs. The analyzed organs can be arranged in the order of decreasing Hg concentration as follows: liver >> kidney >> muscle > spleen ≥ heart ≥ intestine > lung ≥ testis. The mercury concentration values in walruses from the coastal waters off the Chukchi Peninsula are lower than those obtained from walruses in Alaska and the Canadian Arctic. Our findings may provide a basis for the further long-term monitoring of the condition of the Pacific walrus population and pollution of the Arctic ecosystem.

Toxaphene chemistry: separation and characterisation of selected enantiomers of the Polychloropinene mixtures.

The primary goal for the study presented here was the preparation and characterisation of enantiomeric pure chlorobornane standards (Toxaphene). In this context, we partially modeled the procedure for Polychloropinene production in the former USSR. The initial reaction was ionic addition of hydrogen chloride to (1S)-alpha-pinene resulting predominantly in (1S)-2-endo-chlorobornane. Further photochlorination gave mixtures of chlorinated terpenes with different average content of Cl per molecule. The resulting mixtures were separated on a silica-gel column and a number of known hepta to decachlorobornanes were identified in fractions with the help of NMR and GC (using electron capture and mass spectrometric detection)--but in very unusual ratios as compared to the technical Toxaphene mixture formerly produced by Hercules (USA). Also several previously unknown congeners were isolated or detected. Three of the isolated congeners were obtained in crystalline state and X-ray crystallography showed their enantiomeric purity.