Effects of Overweight on Risk of Thyroid Nodules in Children and Adolescents: The Fukushima Health Management Survey.

CONTEXT: Examining how overweight/obesity impacts thyroid nodule development in children and adolescents by sex and age can speculate on the mechanism. OBJECTIVE: We examined whether overweight in children and adolescents are associated with thyroid nodule development by sex and age. DESIGN: Approximately 300,000 participants who underwent thyroid ultrasonography in the Fukushima Health Management Survey after a nuclear accident were enrolled. Those without nodules in the initial two examinations (1-3 and 4-5 years postaccident) were prospectively assessed for nodule development in the third examination (6-7 years postaccident) relative to baseline overweight status, with an average follow-up of 4.2 years. SETTING: A population-based prospective cohort study. PARTICIPANTS: The first and second thyroid examinations involved 299,939 and 237,691 participants, respectively, excluding those with thyroid nodules. After the third examination, 184,519 participants were finalized for analysis. MAIN OUTCOME MEASURES: Multivariable-adjusted odds ratios of new detected thyroid nodules for overweight participants compared with normal-weight participants. RESULTS: New thyroid nodules were detected in 660 participants. Being overweight was positively associated with thyroid nodules. The adjusted odds ratio (95% confidence interval) of thyroid nodules for overweight participants compared with other participants was 1.27 (1.04-1.57). Additionally, the multivariable-adjusted odds ratios for males and females with overweight were 1.21 and 1.32, respectively, and those for different age groups (0-9, 10-14, and 15-19 years) ranged from 1.17 to 1.75. CONCLUSIONS: Being overweight was associated with thyroid nodules in children and adolescents, mostly adolescent females, regardless of their proximity to the nuclear power plant.

In vitro activity of tedizolid against 43 species of Nocardia species.

The purpose of the present study was to evaluate the in vitro activity of tedizolid against several clinically significant species of Nocardia by comparing with that of linezolid. A total of 286 isolates of Nocardia species, including 236 clinical isolates recovered from patients in Japan and 50 strains (43 species) purchased from NITE Biological Resource Center, were studied. Antimicrobial susceptibility testing was performed using the broth microdilution method. For the 286 Nocardia isolates, the minimal inhibitory concentration (MIC)50 and MIC90 values of tedizolid were 0.25 and 0.5 µg/ml, and those of linezolid were 2 and 2 µg/ml, respectively. The distribution of the linezolid/tedizolid ratios (MICs of linezolid/MICs of tedizolid) showed that tedizolid had four- to eight-fold higher activity than linezolid in 96.1% (275/286) of Nocardia isolates. Both the tedizolid and linezolid MIC90 values for Nocardia brasiliensis were two-fold higher than those for the other Nocardia species. Both tedizolid and linezolid had low MIC values, 0.25-1 µg/ml and 0.5-4 µg/ml, respectively, even against nine isolates (five species) that were resistant to trimethoprim/sulfamethoxazole. One Nocardia sputorum isolate showed reduced susceptibility to tedizolid (4 µg/ml). Bioinformatics analysis suggests different resistance mechanisms than the oxazolidinone resistance seen in enterococci and staphylococci.

Prevalence of thyroid diffuse goiter and its association with body mass index and the presence of cysts and nodules in children and adolescents: the Fukushima Health Management Survey.

The main cause of diffuse thyroid goiter is autoimmune chronic thyroiditis, otherwise known as Hashimoto's thyroiditis. Thyroid hormones play pivotal roles in growth and development during childhood. However, the prevalence of diffuse goiter and the relationships between diffuse goiter, thyroid volume, cysts and nodules, and anthropometric measurements in children are not well known. Among 789,459 participants who participated in thyroid ultrasound examinations, 320,206 participants (male: 161,728; female: 158,478) aged 1-23 years were analyzed. Logistic regression analyses were conducted to calculate the odds ratios of the standard deviation score of body mass index (BMI-SDS), the SDS of bilateral width multiplied thickness area (BWTAR-SDS) as a provisional determination of thyroid volume, and the presence of nodules or cysts for positive diffuse goiter compared with negative diffuse goiter after correction for sex and age. The prevalence of diffuse goiter increased in a female-dominant manner with aging. Compared with the absence of diffuse goiter, the age- and sex-adjusted odds ratios (95% confidence intervals) for BMI-SDS (1 SD), BWTAR-SDS (1 SD), cysts, and nodules were 1.24 (1.21-1.27), 3.21 (3.13-3.29), 0.53 (0.50-0.58), and 1.38 (1.17-1.64), respectively. The odds ratios of nodules for positive diffuse goiter were 4.18 (1.08-16.08), 1.76 (1.01-3.07), 1.80 (1.32-2.45), and 1.34 (1.08-1.67) in the age groups 1-7, 8-11, 12-15, and 16-23 years, respectively. The age-dependent increase in the prevalence of diffuse goiter was independently associated with increased BMI and positive prevalence of nodules in young individuals.

A Multicenter Study on the Utility of Selective Enrichment Broth for Detection of Group B Streptococcus in Pregnant Women in Japan.

Universal screening for Streptococcus agalactiae, Group B Streptococcus (GBS), in pregnant women is important for preventing severe infectious diseases in neonates. The subculture method using selective enrichment broth has been reported to significantly improve GBS detection in the US; however, this method is not widely practiced in Japan. An insufficiency of large-scale validation is one of the reasons; therefore, we validated the utility of the subculture method in collaboration with multiple facilities. A total of 1957 vaginal-rectal swab specimens were obtained from pregnant women at 35-37 gestational weeks from March 1, 2020 to August 30, 2020 at Fukushima Medical University Hospital, Aiiku Hospital, Kitano Hospital, and the University of the Ryukyus Hospital. Three methods, such as conventional direct agar plating, subculture using selective enrichment broth, and direct latex agglutination (LA) testing with incubated broth were performed for GBS detection and discrepant results were confirmed using real-time PCR. The GBS detection rates for direct agar plating, subculture, and direct LA testing were 18.2% (357/1957), 21.6% (423/1957), and 22.3% (437/1957), respectively. The use of selective enrichment broth showed results in highly-sensitive GBS detection and is therefore recommended for GBS screening to prevent GBS-related infectious diseases in neonates in Japan.

Confounding factors and biases involved in regional differences in the detection rate of thyroid cancer in the second-round Thyroid Ultrasound Examination: the Fukushima Health Management Survey.

In response to concerns about health due to radiation exposure, the Fukushima Prefecture launched the Thyroid Ultrasound Examination program for residents aged 0-18 years at the time of the earthquake. Herein, we considered the confounding factors involved in the regional differences in the development of thyroid cancer. In this study, the 242 065 individuals who participated in both first- and second-round surveys were classified into four groups by address according to their air radiation dose. The number of participants diagnosed as malignant or suspicious for malignancy by cytological examination were 17, 38, 10 and 4 with detection rates of 53.8, 27.8, 21.7 and 14.5 per 100 000 participants in Regions 1, 2, 3 and 4, respectively. Sex (P = 0.0400), age at the time of the primary examination (P < 0.0001) and interval between the first- and second-round surveys (P < 0.0001) were significantly different among the four regions, and these were suspected to be confounding factors affecting regional differences in malignant nodule detection rates. In addition, significant regional differences were observed in the participation rate in the confirmatory examination (P = 0.0037) and the fine needle aspiration cytology implementation rate (P = 0.0037), which could be potential biases. No significant regional differences in the detection of malignant nodules were found in the multivariate logistic regression analysis after adjusting for the survey interval alone or for sex, age and survey interval. The confounding factors and biases identified in this study that may have important impacts on thyroid cancer detection rate should be fully considered in future studies.

Ultrasonography-based reference values for the cross-sectional area of the thyroid gland in children and adolescents: The Fukushima Health Management Survey.

We previously described the thyroid volume, which was calculated by measuring the thyroid width, thickness, and longitudinal length using ultrasonography, in children and adolescents. We have proposed a simplified method for quantitatively assessing the thyroid size, to overcome the inaccuracy and challenges in measuring the longitudinal length of the thyroid. Based on measurements of 317,847 (girls: 156,913, boys: 160,934) children and adolescents, we calculated sex-specific means and standard deviations of thyroid width and thickness, and of the cross-sectional area computed by multiplying them, for every age and 0.1 m2 of body surface area, after ensuring normal distribution with Box-Cox transformation. Multivariate regression analysis revealed that female sex, age, and body surface area were independently associated with areas of each thyroid lobe. Our novel method may be useful in quantitatively assessing the thyroid size, and appropriately diagnosing pathological conditions, such as hypoplasia, atrophy, and enlargement of the thyroid gland, in children and adolescents.

A Comprehensive Review of the Progress and Evaluation of the Thyroid Ultrasound Examination Program, the Fukushima Health Management Survey.

The Great East Japan Earthquake on March 11, 2011, and the subsequent tsunami caused an accident at the Fukushima Daiichi Nuclear Power Plant, in which extensive damage to the nuclear power reactors resulted in massive radioactive contamination. Fukushima Prefecture implemented the Thyroid Ultrasound Examination (TUE) program as part of the Fukushima Health Management Survey project in response to residents' anxieties about health risks due to radiation exposure for residents aged 0-18 years at the time of the nuclear accident. This program consisted of the primary examination and the confirmatory examination. In the primary examination, thyroid nodules and cysts were examined using portable ultrasound apparatuses. The confirmatory examination was performed to have clinical or cytological diagnosis. As of June 30, 2021, 116, 71, 31, 36, and 9 examinees in the first, second, third, and fourth round of surveys, and the survey at age 25 years, respectively, were determined to have nodules cytologically diagnosed as malignant or suspicious for malignancy. The confirmatory examination of the fourth-round survey and the primary and confirmatory examination of fifth-round survey are currently in progress. Together with the low thyroid absorbed radiation dose estimated in the United Nations Scientific Committee on the Effects of Atomic Radiation 2020 report, our results suggested that the increased incidence of childhood thyroid cancer in Fukushima Prefecture was not caused by radiation exposure, but rather by the highly sensitive detection method. As detailed in this review, there were ongoing challenges in our program, such as actions against the risk of overdiagnosis and psychological support for participants and their families.

Achievements and Current Status of the Fukushima Health Management Survey.

The Fukushima Health Management Survey (FHMS) was established in response to the Fukushima Daiichi Nuclear Power Plant accident on March 11, 2011. The primary objectives of the study are to monitor residents' long-term health and promote their future well-being, and to determine the health effects of long-term low-dose radiation exposure. This special issue summarizes the results and current status of the FHMS and discusses the challenges and future directions of the FHMS. The FHMS, a cohort study of all people who were residents in Fukushima Prefecture at the time of the accident, consists of a Basic Survey, Thyroid Ultrasound Examination, Comprehensive Health Check, Mental Health and Lifestyle Survey, and Pregnancy and Birth Survey. The radiation exposure was estimated based on the behavioral records examined using the Basic Survey. Although the response rate was low in the Basic Survey, the representativeness of the radiation exposure data was confirmed using additional surveys. There appears to be no relationship between the radiation exposure and risk of thyroid cancer, although more thyroid cancer cases were detected than initially expected. The ongoing Comprehensive Health Check and Mental Health and Lifestyle Survey have provided evidence of worsening physical and mental health status. The Pregnancy and Birth Survey showed rates of preterm delivery, low birth weight, and congenital abnormalities similar to the national average. Considering the above evidence, the Fukushima Prefectural Government decided to end the Pregnancy and Birth Survey at the end of March 2021, as recommended by the Prefectural Oversight Committee. The framework of the FHMS has not changed, but the FHMS needs to adapt according to the survey results and the changing needs of the eligible residents and municipalities.

Revisiting the Geographical Distribution of Thyroid Cancer Incidence in Fukushima Prefecture: Analysis of Data From the Second- and Third-round Thyroid Ultrasound Examination.

BACKGROUND: After the first-round (Preliminary Baseline Survey) ultrasound-based examination for thyroid cancer in response to the accident at the Fukushima Daiichi Nuclear Power Plant in 2011, two rounds of surveys (Full-scale Survey) have been carried out in Fukushima Prefecture. Using the data from these surveys, the geographical distribution of thyroid cancer incidence over 6 or 7 years after the disaster was examined. METHODS: Children and adolescents who underwent the ultrasound-based examinations in the second- and/or third-round (Full-scale) survey in addition to the first-round survey were included. With a discrete survival model, we computed age, sex, and body mass index standardized incidence ratios (SIRs) for municipalities. Then, we employed spatial statistics to assess geographic clustering tendency in SIRs and Poisson regression to assess the association of SIRs with the municipal average absorbed dose to the thyroid gland at the 59-municipality level. RESULTS: Throughout the second- and third-round surveys, 99 thyroid cancer cases were diagnosed in the study population of 252,502 individuals. Both flexibly shaped spatial scan statistics and maximized excess events test did not detect statistically significant spatial clustering (P = 0.17 and 0.54, respectively). Poisson regression showed no significant dose-response relationship: the estimated relative risks of lowest, middle-low, middle-high, and highest areas were 1.16 (95% confidence interval [CI], 0.52-2.59), 0.55 (95% CI, 0.31-0.97), 1.05 (95% CI, 0.79-1.40), and 1.24 (95% CI, 0.89-1.74). CONCLUSION: There was no statistical support for geographic clustering or regional association with radiation dose measures of the thyroid cancer incidence in the cohort followed up to the third-round survey (fiscal years 2016-2017) in Fukushima Prefecture.

Ubiquitin-mediated mitochondrial regulation by MITOL/MARCHF5 at a glance.

Mitochondria are involved in various cellular processes, such as energy production, inflammatory responses and cell death. Mitochondrial dysfunction is associated with many age-related diseases, including neurological disorders and heart failure. Mitochondrial quality is strictly maintained by mitochondrial dynamics linked to an adequate supply of phospholipids and other substances from the endoplasmic reticulum (ER). The outer mitochondrial membrane-localized E3 ubiquitin ligase MITOL/MARCHF5 is responsible for mitochondrial quality control through the regulation of mitochondrial dynamics, formation of mitochondria-ER contacts and mitophagy. MITOL deficiency has been shown to impair mitochondrial function, cause an excessive inflammatory response and increase vulnerability to stress, resulting in the exacerbation of the disease. In this study, we overview the ubiquitin-mediated regulation of mitochondrial function by MITOL and the relationship between MITOL and diseases.

Possible Association Between Thyroid Nodule Formation and Developmental Alterations in the Pituitary-Thyroid Hormone Axis in Children and Adolescents: The Fukushima Health Management Survey.

Background: We previously found low thyrotropin (TSH) levels in children and adolescents with thyroid nodules, including papillary thyroid cancer, although it is generally accepted that high TSH levels are a risk factor for formation and growth of thyroid nodules in adults. To clarify the reasons for the discrepancy, we precisely analyzed the features of pituitary-thyroid hormone (TH) actions in children and adolescents with or without nodules at different ages. Methods: Among the 4955 participants who participated in a second screening by thyroid ultrasound examination in the Fukushima Health Management Survey, 721 and 2849 euthyroid participants aged 6-20 years without or with nodules, including thyroid cancer, were selected for evaluation of TH regulation. The responsivity of TSH to THs was assessed by two thyroid feedback quantile-based indices (T4FQI and T3FQI). Logistic regression analyses were conducted to calculate the odds ratios (ORs) of serum concentrations related to thyroid functions for positive thyroid nodules compared with negative nodules. Results: The feedback indices declined in a sex-specific manner with aging. In particular, T3FQI, the index for TSH response to free triiodothyronine (fT3), started to decline after ∼10 and 15 years of age in female and male participants, respectively. Compared with the absence of nodules, the age- and sex-adjusted ORs (confidence intervals) for logTSH, free thyroxine (fT4), fT3, T4FQI, T3FQI, and thyroglobulin levels were 0.586 (0.501-0.685), 1.036 (0.595-1.805), 1.059 (0.842-1.332), 0.569 (0.454-0.715), 0.564 (0.443-0.719), and 1.01 (1.005-1.014), respectively. Associations between the presence of nodules and either low logTSH or low feedback indices were observed in participants aged between 12 and 17 years among the total cohort. Conclusions: The relationships between the levels of TSH and THs changed in a sex-dependent manner in children and adolescents. The age-dependent shift in the pituitary-TH set point may be associated with age-dependent nodule formation during restricted periods of growth and maturation in both young female and male participants.

Matrix-Assisted Laser Desorption Ionization-Time-of-Flight Mass Spectrometry with Time-of-Flight Peak Analysis for Rapid and Accurate Detection of Group B Streptococcus in Pregnant Women.

Severe infections in neonates caused by Streptococcus agalactiae, Group B Streptococcus (GBS), are often associated with GBS transmission from their mothers during labor or birth. Hence, it is necessary to develop a universal method for screening vaginal-rectal GBS colonization in pregnant women worldwide. A subculture of vaginal-rectal swabs using a selective enrichment broth and an agar plate is conventionally recommended for GBS screening. However, infants born to mothers who are GBS negative on subculture sometimes contract GBS infections. Therefore, we developed another method with high sensitivity for GBS screening. A total of 178 vaginal-rectal swabs from pregnant women were inoculated into the enrichment broth, of which 126 were suspected of containing GBS due to the change in the color of the broth. The subculture results were positive for GBS in 34 (27.0%) swabs. Each broth was then analyzed using matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS). Analysis of the TOF peaks specific to GBS revealed 45 (35.7%) swabs as GBS positive. Of the 11 GBS positive samples on TOF peak analysis but negative on subculture, S. agalactiae gene targets were detected through PCR in 4 samples. MALDI detection with analysis of peaks of TOF (MDAPT) can detect GBS directly from cultured broth with high sensitivity. MDAPT can be an alternative method for GBS screening in pregnant women and contribute to the prevention of severe GBS infectious diseases in neonates. IMPORTANCE As previously reported, 10%-30% of pregnant women carry Streptococcus agalactiae, Group B Streptococcus (GBS), in their vagina or rectum, and approximately 50% of them vertically transmit GBS to their neonates during labor or birth. Moreover, 1%-2% of the GBS-transmitted neonates develop severe GBS infectious diseases, which have a mortality rate of 19.2% in a preterm infant and 2.1% in a full-term infant. Hence, universal screening for GBS colonization in pregnant women is conducted worldwide using the subculture procedure; however, infants born to GBS negative mothers sometimes contract GBS infections. Therefore, other laboratory techniques are required for detecting GBS more accurately. The proposed method "MALDI detection with analysis of peaks of TOF (MDAPT)" detects GBS directly from cultured broth with high sensitivity. Therefore, it can be an alternative method for GBS screening in pregnant women, thereby contributing to the prevention of severe GBS infectious diseases in neonates.

NKX2-1 re-expression induces cell death through apoptosis and necrosis in dedifferentiated thyroid carcinoma cells.

NK2 homeobox 1 (NKX2-1) is a thyroid transcription factor essential for proper thyroid formation and maintaining its physiological function. In thyroid cancer, NKX2-1 expression decreases in parallel with declined differentiation. However, the molecular pathways and mechanisms connecting NKX2-1 to thyroid cancer phenotypes are largely unknown. This study aimed to examine the effects of NKX2-1 re-expression on dedifferentiated thyroid cancer cell death and explore the underlying mechanisms. A human papillary thyroid carcinoma cell line lacking NKX2-1 expression was infected with an adenoviral vector containing Nkx2-1. Cell viability decreased after Nkx2-1 transduction and apoptosis and necrosis were detected. Arginase 2 (ARG2), regulator of G protein signaling 4 (RGS4), and RGS5 mRNA expression was greatly increased in Nkx2-1-transducted cells. After suppressing these genes by siRNA, cell death, apoptosis, and necrosis decreased in RGS4 knockdown cells. These findings demonstrated that cell death was induced via apoptosis and necrosis by NKX2-1 re-expression and involves RGS4.

Fine Needle Aspiration Cytology Implementation and Malignancy Rates in Children and Adolescents Based on Japanese Guidelines: The Fukushima Health Management Survey.

Background: The thyroid ultrasound examination (TUE) program was initiated among the residents of Fukushima Prefecture aged ≤18 years at the time of the Fukushima Dai-ichi Nuclear Power Plant accident. In this program, fine needle aspiration cytology (FNAC) was performed only in cases that conformed to the Japanese guidelines for the management of thyroid nodules. To analyze the suitability of the protocol in the TUE, we analyzed the implementation rate of FNAC and the detection rate of thyroid malignancy. Methods: There were 299,939 and 269,659 voluntary participants in the Preliminarily Baseline Survey (PLBS), first-round survey, and the first Full-scale Survey (FSS), second-round survey, of the TUE, respectively. FNAC is recommended for nodules with diameters 5.1-10.0 mm showing sonographic characteristics that are strongly suspicious for thyroid carcinoma; diameters 10.1-20.0 mm with characteristics that are suspicious for carcinoma; and all nodules with diameters >20 mm. Results: In the PLBS and the first FSS, 1362 and 1382 cases with thyroid nodules sized ≥5.1 mm in diameter were found, respectively. The implementation rates of FNAC in the PLBS were 20.1%, 63.2%, and 87.7% of subjects with nodules sized 5.1-10.0, 10.1-20.0, and ≥20.1 mm in diameter, respectively. In the first FSS, the FNAC implementation rates were 7.3%, 26.0%, and 50.0% in the subjects with nodules with diameters 5.1-10.0, 10.1-20.0, and ≥20.1 mm, respectively. In the subjects who underwent FNAC, the detection rates of malignant and suspected malignant nodules were 21.4% and 34.1% in the PLBS and first FSS, respectively. In the first FSS, malignant or suspected malignant nodules were found in 0.63% and 0.40% of subjects who had nodules of diameters ≤5.0 mm and 5.1-10.0 mm in the PLBS, respectively. In contrast, in the subjects with nodules measuring ≥10.0 mm in diameter in the PLBS, no malignancies were detected. Conclusions: The use of a protocol that conformed to the Japanese guidelines led to a reduction in the FNAC implementation rate and an increase in the malignancy detection rate in smaller nodules. In addition, the use of this strategy enabled us to avoid detection failure of thyroid carcinomas >10.0 mm.

Diagnostic Strategies for Thyroid Nodules Based on Ultrasonographic Findings in Japan.

In recent years, the incidence of thyroid cancer has been increasing worldwide, which is believed to be mainly due to the widespread use of imaging examinations, such as ultrasonography. In this context, ultrasonography has become increasingly important because it can evaluate not only the presence or absence of nodules, but also the detailed characteristics of the nodule, making it possible to diagnose benign or malignant nodules before cytology is performed. In Japan, the third edition of the sonographic diagnostic criteria for thyroid nodules is currently widely used, and its content is similar to that of recent meta-analyses and guidelines from medical societies in other countries. In addition, since overdiagnosis of very-low-risk thyroid cancer has recently become an issue, criteria for the implementation of fine needle aspiration cytology (FNAC) have been published by various countries. The Japan Society of Breast and Thyroid Sonology provides guidelines for FNAC implementation for solid and cystic nodules. In the United States, the ATA, NCCA, and ACR have published guidelines, whereas in Europe, the ESMO and ETA have done the same. All of these guidelines used to classify risk are based on nodule size and sonographic findings. This article outlines the diagnostic criteria and management guidelines in Japan in comparison with those published in other countries. Case studies using actual images were also performed to examine the differences in the FNAC guidelines.

Psychosocial support for the examinees and their families during the secondary confirmatory examination:Analyses of support records at first visit.

Background and Purpose The Thyroid Ultrasound Examination (TUE) program is conducted as part of the Fukushima Health Management Survey. Following the established criteria, examinees are called in for a secondary confirmation examination, which may induce high anxiety related to a thyroid cancer for both the examinees and their families. Therefore, Fukushima Medical University created the Thyroid Support Team to reduce anxiety. The purpose of this study is to analyze the psychosocial support for examinees and their families through two types of records, and to clarify the current issues and determine future directions of support.Materials and methods We analyzed 223 records of support for the first visit of examinees who attended the secondary confirmatory examination, conducted at Fukushima Medical University from September 2018 to March 2019.Results During the first visit, frequent topics and questions brought up by the examinees and their families were about the "Thyroid Ultrasound Examination (TUE) program" and "Examination findings". The Thyroid Support Team members assisted them by "Responding to questions", "Confirming the doctor's explanation" and "Providing information". The percentage of people with high anxiety decreased in both examinees and their family members after the examination. The level of anxiety was lower among those who had already taken the secondary confirmatory examination. Family members' anxiety was significantly higher than that of the examinees, and anxiety levels were highly correlated between examinees and their families.Conclusion The psychosocial support for examinees and their families was important in reducing their anxiety.　Currently there are changes in social conditions and various opinions concerning the TUE.　Thus, careful explanation and the need for decision-making supports for the examinees and their families increased. Also, we should take into account the aging of the examinees and expanding the available psychosocial support.

Identification and antimicrobial susceptibility profiles of Nocardia species clinically isolated in Japan.

The aims of the present study were to profile the antimicrobial susceptibility patterns of a diverse range of Nocardia species isolated in Japan, and to determine the ability of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) for species/complex identification. Identification of 153 clinical isolates was performed by full-length 16S rRNA gene sequencing as a reference method to evaluate the usefulness of MALDI-TOF MS identification. Antimicrobial susceptibility testing (AST) for 14 antibiotics was performed using the broth microdilution method against 146 of the isolates. Among the total 153 clinical isolates, Nocardia farcinica complex (25%) was the most common species, followed by Nocardia cyriacigeorgica (18%), Nocardia brasiliensis (9%), Nocardia nova (8%), and Nocardia otitidiscaviarum (7%). Among 150 isolates identified to the species/complex level by 16S rRNA gene sequencing, MALDI-TOF MS with the use of a supplemental Nocardia library (JMLD library ver.ML01) correctly identified 97.3% (n = 146) to the species/complex level and 1.3% (n = 2) to the genus level. Among the 146 Nocardia isolates that underwent AST, the susceptibilities were 100% to linezolid, 96% to amikacin, 94% to trimethoprim-sulfamethoxazole, and 76% to imipenem. None of the trimethoprim-sulfamethoxazole-resistant isolates carried either plasmid-mediated sulfonamide-resistant genes (sul1, sul2) or trimethoprim-resistant genes (dfrA).

Introduction of histological classification and cytology reporting format of the Japanese General Rules for the Description of Thyroid Cancer with a special focus on the differences of the WHO Histological Classification and The Bethesda System of Thyroid Cytology.

Histological classification and cytology reporting format described in General Rules for the Description of Thyroid Cancer, the 8th edition (2019) (the Japanese General Rules) were briefly introduced. Moreover, the differences between "the Japanese General Rules", and WHO Histological Classification, the 4th edition (2017) and The Bethesda System for Reporting Thyroid Cytopathology, the 2nd edition (2018) were also explained. The Japanese General Rules did not accept the borderline lesions of thyroid tumor which were newly shown in WHO Histological Classification. We believe it is not necessary to introduce these borderline lesions in daily practice in Japan. Borderline lesions were proposed for avoiding over-surgery for thyroid cancer patients. In the United States, when the patient is diagnosed as malignant on cytology, total thyroidectomy is generally recommended. However, there is no over-surgery in Japan, because surgeons have several choices of treatment for thyroid cancer patients. This article is the first that the Japanese General Rules was shown by foreign language. Therefore, this will be advantageous to us when we present our opinion concerning histology and cytology of thyroid tumor to the world.

Forebrain-specific deficiency of the GTPase CRAG/Centaurin-γ3 leads to immature dentate gyri and hyperactivity in mice.

Mouse models of various neuropsychiatric disorders, such as schizophrenia, often display an immature dentate gyrus, characterized by increased numbers of immature neurons and neuronal progenitors and a dearth of mature neurons. We previously demonstrated that the CRMP5-associated GTPase (CRAG), a short splice variant of Centaurin-γ3/AGAP3, is highly expressed in the dentate gyrus. CRAG promotes cell survival and antioxidant defense by inducing the activation of serum response factors at promyelocytic leukemia protein bodies, which are nuclear stress-responsive domains, during neuronal development. However, the physiological role of CRAG in neuronal development remains unknown. Here, we analyzed the role of CRAG using dorsal forebrain-specific CRAG/Centaurin-γ3 knockout mice. The mice revealed maturational abnormality of the hippocampal granule cells, including increased doublecortin-positive immature neurons and decreased calbindin-positive mature neurons, a typical phenotype of immature dentate gyri. Furthermore, the mice displayed hyperactivity in the open-field test, a common measure of exploratory behavior, suggesting that these mice may serve as a novel model for neuropsychiatric disorder associated with hyperactivity. Thus, we conclude that CRAG is required for the maturation of neurons in the dentate gyrus, raising the possibility that its deficiency might promote the development of psychiatric disorders in humans.