Cultural adaptation, content, and protocol of a feasibility study of school-based "Let's learn about emotions" intervention for Finnish primary school children.

Introduction: Emotional awareness and emotion regulation are crucial for cognitive and socio-emotional development in children. School-based interventions on socio-emotional skills have the potential to prevent these problems and promote well-being of children. The Japanese school-based program, Universal Unified Prevention Program for Diverse Disorders (Up2-D2), has shown preventive effects on mental health of children in Japan. The aims of this protocol paper are to describe the unique process of adapting the Up2-D2 from Eastern to Western context, and to present a feasibility study of the intervention, conducted in Finland. Methods: The cultural adaptation process started with the linguistic translation of materials, followed by the modification of language to fit the Finnish context. While the Japanese ideology was saved, some content was adapted to fit Finnish school children. Further modifications were made based on feedback from pupils and teachers. The Finnish version of the program was named "Let's learn about emotions" and consisted of 12 sessions and targeted 8- to 12-year-old pupils. A teacher education plan was established to assist Finnish teachers with the intervention, including a workshop, teachers' manual, brief introductory videos, and online support sessions. A feasibility study involving 512 4th graders in the City of Hyvinkää, South of Finland, was conducted. It assessed emotional and behavioral problems, classroom climate, bullying, loneliness, perception of school environment, knowledge of emotional awareness, and program acceptability. Discussion: The originality of this study underlies in the East-West adaptation of a cognitive behavioral therapy-based program. If promising feasibility findings are replicated in Finland, it could pave the way for further research on implementing such programs in diverse contexts and cultures, promoting coping skills, awareness, social skills and early prevention of child mental health problems. Ethics: The ethical board of the University of Turku gave ethics approval for this research. The educational board of the City of Hyvinkää accepted this study.

Effects of Rice Wine Lees on Cognitive Function in Community-Dwelling Physically Active Older Adults: A Pilot Randomized Controlled Trial.

BACKGROUND: Rice wine lees (RWL), a Japanese traditional fermented product, is a rich source of one-carbon metabolism-related nutrients, which may have beneficial effects on cognitive function. OBJECTIVES: We aimed to examine the effect of the RWL on cognitive function in community-dwelling physically active older adults. DESIGN: Double-blind, randomized, placebo-controlled study (clinical trial number: UMIN 000027158). SETTING: Community-based intervention including assessments conducted at the University of Hyogo and a public liberal arts school in Himeji City, Japan. PARTICIPANTS: A total of 35 community-dwelling older adults (68-80 years) who performed mild exercise before and during the trial were assigned to either the RWL (n=17) or the placebo group (n=18). INTERVENTION: Daily consumption of 50 g RWL powder, which contained one-carbon metabolism-related nutrients, or the placebo powder (made from soy protein and dextrin) for 12 weeks. Both supplements included equivalent amounts of energy and protein. MEASUREMENTS: Montreal Cognitive Assessment, computerized cognitive function test, and measurements of serum predictive biomarkers (transthyretin, apolipoprotein A1, and complement C3) were conducted at baseline and follow-up. RESULTS: Visual selective attention and serum transthyretin significantly improved in the RWL group, whereas there was no significant change in the placebo group. No significant group difference was observed in the remaining cognitive performance tests. CONCLUSIONS: RWL supplements seem to have a few effects on cognitive function in community-dwelling physically active older adults. However, the impact was limited; therefore, further studies with sufficient sample size are warranted to elucidate this issue.

Aneuploid rescue precedes X-chromosome inactivation and increases the incidence of its skewness by reducing the size of the embryonic progenitor cell pool.

STUDY QUESTION: Do monosomy rescue (MR) and trisomy rescue (TR) in preimplantation human embryos affect other developmental processes, such as X-chromosome inactivation (XCI)? SUMMARY ANSWER: Aneuploid rescue precedes XCI and increases the incidence of XCI skewness by reducing the size of the embryonic progenitor cell pools. WHAT IS KNOWN ALREADY: More than half of preimplantation human embryos harbor aneuploid cells, some of which can be spontaneously corrected through MR or TR. XCI in females is an indispensable process, which is predicted to start at the early-blastocyst phase. STUDY DESIGN, SIZE, DURATION: We examined the frequency of XCI skewness in young females who carried full uniparental disomy (UPD) resulting from MR or TR/gamete complementation (GC). The results were statistically analyzed using a theoretical model in which XCI involves various numbers of embryonic progenitor cells. PARTICIPANTS/MATERIALS, SETTING, METHODS: We studied 39 children and young adults ascertained by imprinting disorders. XCI ratios were determined by DNA methylation analysis of a polymorphic locus in the androgen receptor gene. We used Bayesian approach to assess the probability of the occurrence of extreme XCI skewness in the MR and TR/GC groups using a theoretical model of 1-12 cell pools. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 12 of 39 individuals (31%) showed skewed XCI. Extreme skewness was observed in 3 of 15 MR cases (20%) and 1 of 24 TR/GC cases (4.2%). Statistical analysis indicated that XCI in the MR group was likely to have occurred when the blastocyst contained three or four euploid embryonic progenitor cells. The estimated size of the embryonic progenitor cell pools was approximately one-third or one-fourth of the predicted size of normal embryos. The TR/GC group likely had a larger pool size at the onset of XCI, although the results remained inconclusive. LIMITATIONS, REASONS FOR CAUTION: This is an observational study and needs to be validated by experimental analyses. WIDER IMPLICATIONS OF THE FINDINGS: This study provides evidence that the onset of XCI is determined by an intrinsic clock, irrespectively of the number of embryonic progenitor cells. Our findings can also be applied to individuals without UPD or imprinting disorders. This study provides a clue to understand chromosomal and cellular dynamics in the first few days of human development, their effects on XCI skewing and the possible implications for the expression of X-linked diseases in females. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the Grants-in-aid for Scientific Research on Innovative Areas (17H06428) and for Scientific Research (B) (17H03616) from Japan Society for the Promotion of Science (JSPS), and grants from Japan Agency for Medical Research and Development (AMED) (18ek0109266h0002 and 18ek0109278h0002), National Center for Child Health and Development and Takeda Science Foundation. The authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: Not applicable.

Paternal height has an impact on birth weight of their offspring in a Japanese population: the Japan Environment and Children's Study.

This study examines the relationship between paternal height or body mass index (BMI) and birth weight of their offspring in a Japanese general population. The sample included 33,448 pregnant Japanese women and used fixed data, including maternal, paternal and infant characteristics, from the Japan Environment and Children's Study (JECS), an ongoing nationwide birth cohort study. Relationships between paternal height or BMI and infant birth weight [i.e., small for gestational age (SGA) and large for gestational age (LGA)] were examined using a multinomial logistic regression model. Since fetal programming may be a sex-specific process, male and female infants were analyzed separately. Multivariate analysis showed that the higher the paternal height, the higher the odds of LGA and the lower the odds of SGA in both male and female infants. The effects of paternal BMI on the odds of both SGA and LGA in male infants were similar to those of paternal height; however, paternal height had a stronger impact than BMI on the odds of male LGA. In addition, paternal BMI showed no association with the odds of SGA and only a weak association with the odds of LGA in female infants. This cohort study showed that paternal height was associated with birth weight of their offspring and had stronger effects than paternal BMI, suggesting that the impact of paternal height on infant birth weight could be explained by genetic factors. The sex-dependent effect of paternal BMI on infant birth weight may be due to epigenetic effects.

The effectiveness of bismuth breast shielding with protocol optimization in CT Thorax examination.

BACKGROUND: Numerous techniques had been proposed to reduce radiation exposure in computed tomography (CT) including the use of radiation shielding. OBJECTIVE: This study aims to evaluate efficacy of using a bismuth breast shield and optimized scanning parameter to reduce breast absorbed doses from CT thorax examination. METHODS: Five protocols comprising the standard CT thorax clinical protocol (CP1) and four modified protocols (CP2 to CP5) were applied in anthropomorphic phantom scans. The phantom was configured as a female by placing a breast component on the chest. The breast component was divided into four quadrants, where 2 thermoluminescence dosimeters (TLD-100) were inserted into each quadrant to measure the absorbed dose. The bismuth shield was placed over the breast component during CP4 and CP5 scans. RESULTS: The pattern of absorbed doses in each breast and quadrant were approximately the same for all protocols, where the 4th quadrant > 3rd quadrant > 2nd quadrant > 1st quadrant. The mean absorbed dose value in CP3 was reduced to almost 34% of CP1's mean absorbed dose. It was reduced even lower to 15% of CP1's mean absorbed dose when the breast shield was used in CP5. CONCLUSION: This study showed that CT radiation exposure on the breast could be reduced by using a bismuth shield and low tube potential protocol without compromising the image quality.

Decreased Incidence of Acute Cellular Rejection in Low-Muscle-Mass Recipients After Living-donor Liver Transplantation.

BACKGROUND: Sarcopenia has recently been studied as a potential risk factor for mortality and complications after liver transplantation. We investigated the impact of low muscle mass on postoperative outcomes after living-donor liver transplantation. METHODS: Our study population consisted of 100 adult recipients who underwent living-donor liver transplantation in our department between 2005 and 2017. Recipients were divided into a low-muscle-mass group (L group) and a normal-muscle-mass group (N group) based on skeletal muscle index (SMI) values, and postoperative outcomes were compared between the groups. Regarding factors that were significantly different between the groups, multivariate analyses were performed to identify predictive factors. RESULTS: Based on the SMI definition, 47 and 53 of the recipients were categorized as having low muscle mass (L group) and normal muscle mass (N group), respectively. Comparison between the groups revealed a significantly reduced incidence of rejection (10.6% in L group vs 30.2% in N group, P = .017) and increased incidences of bacterial infection (61.7% in L group vs 37.7% in N group, P = .017) in the L group compared with the N group. The survival rate did not differ significantly between the groups. Multivariate analyses indicated that muscle mass was a significant predictive factor for both rejection and bacterial infection. CONCLUSION: It is important to recognize that muscle mass has an impact not only on bacterial infection but also on rejection in recipients with low muscle mass in the postoperative course of living-donor liver transplantation.

Population pharmacokinetics and pharmacodynamics of mycophenolic acid using the prospective data in patients undergoing hematopoietic stem cell transplantation.

Mycophenolate mofetil (MMF), a prodrug of mycophenolic acid (MPA), is used to suppress GvHD in patients undergoing hematopoietic stem cell transplantation (HCT). The purpose of this study was to construct a population pharmacokinetic and pharmacodynamic model in HCT patients for individualized MPA therapy. Blood samples were obtained from 49 HCT patients after starting MMF therapy. Population pharmacokinetic and pharmacodynamic parameters were obtained using the program NONMEM. MPA was described via a one-compartment model with a first-order elimination, and 30.9% of MPA glucuronide (MPAG) was found in the enterohepatic circulation. Inosine-5'-monophosphate dehydrogenase (IMPDH) activity was modeled as a maximal inhibitory model with a half-maximal inhibitory concentration (IC50) of 3.59 µg/mL against MPA concentrations. Simulations based on the obtained pharmacokinetic and pharmacodynamic parameters revealed that decreased creatinine clearance increases the MPAG concentration followed by an increased MPA concentration; therefore, IMPDH activity decreases. Diarrhea decreases the enterohepatic circulation of MPAG and consequently reduces MPA concentration. The IC50 for MPA exhibited a positive association with C-reactive protein. Dosage adjustment based on plasma MPA concentration is required especially for patients with renal dysfunction and/or diarrhea.

Efficacy of protocol-based pharmacotherapy management on anticoagulation with warfarin for patients with cardiovascular surgery.

WHAT IS KNOWN AND OBJECTIVE: Anticoagulation therapy with warfarin requires periodic monitoring of prothrombin time-international normalized ratio (PT-INR) and adequate dose adjustments based on the data to minimize the risk of bleeding and thromboembolic events. In our hospital, we have developed protocol-based pharmaceutical care, which we called protocol-based pharmacotherapy management (PBPM), for warfarin therapy. The protocol requires pharmacists to manage timing of blood sampling for measuring PT-INR and warfarin dosage determination based on an algorithm. This study evaluated the efficacy of PBPM in warfarin therapy by comparing to conventional pharmaceutical care. METHODS: From October 2013 to June 2015, a total of 134 hospitalized patients who underwent cardiovascular surgeries received post-operative warfarin therapy. The early series of patients received warfarin therapy as the conventional care (control group, n=77), whereas the latter received warfarin therapy based on the PBPM (PBPM group, n=68). These patients formed the cohort of the present study and were retrospectively analysed. RESULTS: The indications for warfarin included aortic valve replacement (n=56), mitral valve replacement (n=4), mitral valve plasty (n=22) and atrial fibrillation (n=29). There were no differences in patients' characteristics between both groups. The percentage time in therapeutic range in the first 10 days was significantly higher in the PBPM group (47.1%) than that in the control group (34.4%, P<.005). The average time to reach the steady state was significantly (P<.005) shorter in the PBPM group compared to the control group (7.3 vs 8.6 days). WHAT IS NEW AND CONCLUSION: Warfarin therapy based on our novel PBPM was clinically safe and resulted in significantly better anticoagulation control compared to conventional care.

Catastrophic cellular events leading to complex chromosomal rearrangements in the germline.

Although complex chromosomal rearrangements were thought to reflect the accumulation of DNA damage over time, recent studies have shown that such rearrangements frequently arise from 'all-at-once' catastrophic cellular events. These events, designated chromothripsis, chromoanasynthesis, and chromoanagenesis, were first documented in the cancer genome and subsequently observed in the germline. These events likely result from micronucleus-mediated chromosomal shattering and subsequent random reassembly of DNA fragments, although several other mechanisms have also been proposed. Typically, only one or a few chromosomes of paternal origin are affected per event. These events can produce intrachromosomal deletions, duplications, inversions, and translocations, as well as interchromosomal translocations. Germline complex rearrangements of autosomes often result in developmental delay and dysmorphic features, whereas X chromosomal rearrangements are usually associated with relatively mild clinical manifestations. The concept of these catastrophic events provides novel insights into the etiology of human genomic disorders. This review introduces the molecular characteristics and phenotypic outcomes of catastrophic cellular events in the germline.

Organ Perfusion for Uterus Transplantation in Non-Human Primates With Assumed Procurement of a Uterus From a Brain-Dead Donor.

BACKGROUND: Clinical studies of uterus transplantation have been performed to treat uterine factor infertility. Because the uterus is a pelvic visceral organ, the method of perfusion for the procurement of vital organs from a brain-dead donor should be modified for removal of the uterus. Herein, we report the results of a preliminary study in cynomolgus monkeys of a new perfusion method for uterus transplantation with assumed procurement of a uterus from a brain-dead donor. METHODS: Cynomolgus monkeys were used; thoracolaparotomy was performed on the donor. A perfusion catheter was then placed into the unilateral femoral artery and/or external iliac artery. Cross-clamping was performed for the aorta under the diaphragm and the inferior vena cava was divided in the pleural space. The perfusion solution was then administered via the catheter to perfuse all organs in the abdominal cavity, including those in the pelvic cavity. After the perfusion, gross observation and histopathological examination of abdominal organs were conducted. RESULTS: Gross findings showed that all abdominal organs turned white in all specimens, indicating favorable perfusion of the uterus and all other organs in the abdomen. Pathological findings showed that almost no hemocytes were observed in the vessels of each organ. CONCLUSIONS: With perfusion via the femoral artery and/or external iliac artery, all organs in the abdominal cavity, including the uterus, could be perfused. It was suggested that this technique could be useful for uterus transplantation assuming the procurement of a uterus from a brain-dead donor.

Risk assessment of medically assisted reproduction and advanced maternal ages in the development of Prader-Willi syndrome due to UPD(15)mat.

Recent studies have suggested that disomic oocyte-mediated uniparental disomy 15 (UPD(15)mat) is increased in patients with Prader-Willi syndrome (PWS) born after medically assisted reproduction (MAR). However, it remains unknown whether the increase is primarily due to MAR procedure itself or advanced maternal childbearing ages as a predisposing factor for the disomic oocyte production. To examine this matter, we studied 122 naturally conceived PWS patients (PWS-NC group) and 13 MAR-conceived patients (PWS-MAR group). The relative frequency of disomic oocyte-mediated UPD(15)mat was significantly higher in PWS-MAR group than in PWS-NC group (7/13 vs 20/122, p = 0.0045), and the maternal childbearing ages were significantly higher in PWS-MAR group than in PWS-NC group [median (range), 38 (26-45) vs 30 (19-42), p = 0.0015]. However, the logistic regression analysis revealed no significant association between the occurrence of disomic oocyte-mediated UPD(15)mat and MAR, after adjusting for childbearing age (p = 0.25). Consistent with this, while the frequency of assisted reproductive technology (ART)-conceived livebirths was higher in the PWS patients than in the Japanese general population (6.4% vs 1.1%, p = 0.00018), the distribution of childbearing ages was significantly skewed to the increased ages in the PWS patients (p < 2.2 × 10(-16) ). These results argue against a positive association of MAR procedure itself with the development of UPD(15)mat.

Liver-Regenerative Transplantation: Regrow and Reset.

Liver transplantation, either a partial liver from a living or deceased donor or a whole liver from a deceased donor, is the only curative therapy for severe end-stage liver disease. Only one-third of those on the liver transplant waiting list will be transplanted, and the demand for livers is projected to increase 23% in the next 20 years. Consequently, organ availability is an absolute constraint on the number of liver transplants that can be performed. Regenerative therapies aim to enhance liver tissue repair and regeneration by any means available (cell repopulation, tissue engineering, biomaterials, proteins, small molecules, and genes). Recent experimental work suggests that liver repopulation and engineered liver tissue are best suited to the task if an unlimited availability of functional induced pluripotent stem (iPS)-derived liver cells can be achieved. The derivation of iPS cells by reprogramming cell fate has opened up new lines of investigation, for instance, the generation of iPS-derived xenogeneic organs or the possibility of simply inducing the liver to reprogram its own hepatocyte function after injury. We reviewed current knowledge about liver repopulation, generation of engineered livers and reprogramming of liver function. We also discussed the numerous barriers that have to be overcome for clinical implementation.

A silicon nanocrystal/polymer nanocomposite as a down-conversion layer in organic and hybrid solar cells.

Silicon nanocrystal (Si-nc) down-conversion is demonstrated to enhance organic and hybrid organic/inorganic bulk heterojunction solar cells based on PTB7:[70]PCBM bulk heterojunction devices. Surfactant free surface-engineered Si-ncs can be integrated into the device architecture to be optically active and provide a means of effective down-conversion of blue photons (high energy photons below ∼450 nm) into red photons (above ∼680 nm) leading to 24% enhancement of the photocurrent under concentrated sunlight. We also demonstrate that the down-conversion effect under 1-sun is enhanced in the case of hybrid solar cells where engineered Si-ncs are also included in the active layer.

Abnormalities in chromosome 6q24 as a cause of early-onset, non-obese, non-autoimmune diabetes mellitus without history of neonatal diabetes.

AIMS: Abnormalities in the imprinted locus on chromosome 6q24 are the most common causes of transient neonatal diabetes mellitus (6q24-related transient neonatal diabetes). 6q24-Related transient neonatal diabetes is characterized by the patient being small-for-gestational age, diabetes mellitus at birth, spontaneous remission within the first few months and frequent recurrence of diabetes after childhood. However, it is not clear whether individuals with 6q24 abnormalities invariably develop transient neonatal diabetes. This study explored the possibility that 6q24 abnormalities might cause early-onset, non-autoimmune diabetes without transient neonatal diabetes. METHODS: The 6q24 imprinted locus was screened for abnormalities in 113 Japanese patients with early-onset, non-obese, non-autoimmune diabetes mellitus who tested negative for mutations in the common maturation-onset diabetes of the young (MODY) genes and without a history of transient neonatal diabetes. Positive patients were further analysed by combined loss of heterozygosity / comparative genomic hybridization analysis and by microsatellite analysis. Detailed clinical data were collected through the medical records of the treating hospitals. RESULTS: Three patients with paternal uniparental isodisomy of chromosome 6q24 were identified. None presented with hyperglycaemia in the neonatal period. Characteristically, these patients were born small-for-gestational age, representing 27.2% of the 11 patients whose birth weight standard deviation score (SDS) for gestational age was below -2.0. CONCLUSIONS: Abnormalities in the imprinted locus on chromosome 6q24 do not necessarily cause transient neonatal diabetes. Non-penetrant 6q24-related diabetes could be an underestimated cause of early-onset, non-autoimmune diabetes in patients who are not obese and born small-for-gestational age.

Assessment of four methodologies (microparticle enzyme immunoassay, chemiluminescent enzyme immunoassay, affinity column-mediated immunoassay, and flow injection assay-tandem mass spectrometry) for measuring tacrolimus blood concentration in Japanese liver transplant recipients.

Therapeutic drug monitoring (TDM) and subsequent dosage adjustment for individual patients in the treatment with tacrolimus are required after liver transplantation to prevent rejection and over-immunosuppression, which leads to severe infection and adverse reactions including nephrotoxicity. The purpose of this study was to evaluate the analytical performance among commercially available immunoassay methods, which were microparticle enzyme immunoassay (MEIA), chemiluminescent enzyme immunoassay (CLIA), and affinity column-mediated immunoassay (ACMIA), compared with an assay using liquid chromatography-tandem mass spectrometry (LC-MS/MS). In addition, the flow injection assay (FIA-MS/MS) was also evaluated to determine whether it could be available as a new method of analysis in tacrolimus therapy. The blood tacrolimus concentrations in samples from liver transplant recipients (n = 102) were measured using MEIA, CLIA, ACMIA, and LC-MS/MS. Additional blood samples from liver transplant recipients (n = 54) were analyzed using both FIA-MS/MS and LC-MS/MS. Because the assay performance and characteristics of MEIA, CLIA, ACMIA, and FIA-MS/MS are relatively different, the measured data should be carefully considered depending on the methodology.

Itraconazole prophylaxis for invasive Aspergillus infection in lung transplantation.

Invasive Aspergillus infection (IA) is a significant cause of morbidity in lung transplantation (LT). However, its optimal prophylaxis is unclear. We routinely administer itraconazole (ITCZ) prophylaxis to all patients undergoing LT. In this study, we retrospectively evaluated the duration of prophylaxis and risk factors of IA. Among 30 adult patients who underwent LT, 5 patients developed IA. All patients with IA stopped ITCZ treatment within 1 year. At least 1 year of ITCZ prophylaxis is essential for the prevention of IA. Cytomegalovirus infection, renal replacement therapy, and tracheotomy were risk factors for IA.

A novel de novo point mutation of the OCT-binding site in the IGF2/H19-imprinting control region in a Beckwith-Wiedemann syndrome patient.

The IGF2/H19-imprinting control region (ICR1) functions as an insulator to methylation-sensitive binding of CTCF protein, and regulates imprinted expression of IGF2 and H19 in a parental origin-specific manner. ICR1 methylation defects cause abnormal expression of imprinted genes, leading to Beckwith-Wiedemann syndrome (BWS) or Silver-Russell syndrome (SRS). Not only ICR1 microdeletions involving the CTCF-binding site, but also point mutations and a small deletion of the OCT-binding site have been shown to trigger methylation defects in BWS. Here, mutational analysis of ICR1 in 11 BWS and 12 SRS patients with ICR1 methylation defects revealed a novel de novo point mutation of the OCT-binding site on the maternal allele in one BWS patient. In BWS, all reported mutations and the small deletion of the OCT-binding site, including our case, have occurred within repeat A2. These findings indicate that the OCT-binding site is important for maintaining an unmethylated status of maternal ICR1 in early embryogenesis.

Cell type-dependent agonist/antagonist activities of polybrominated diphenyl ethers.

There have been many concerns expressed regarding the possible adverse effects of thyroid hormone-disrupting chemicals including polychlorinated biphenyls and polybrominated diphenyl ethers (PBDEs), since thyroid hormones play crucial roles in normal vertebrate development. A vast amount of PBDEs have been used as flame retardants for the last two decades and our environment has been contaminated with them. Some PBDEs, especially hydroxylated PBDEs, reportedly show an affinity to the thyroid hormone receptor (TR) and act as thyroid hormone agonists, but in other studies they were reported to inhibit the actions of thyroid hormones. Therefore, in the present study, we investigated the binding affinities of PBDEs and their metabolites to TR and their ability to induce thyroid hormone-responsive transcription using luciferase reporter gene assays in two different cell lines, a pituitary cell line, MtT/E-2, and Chinese hamster ovary (CHO) cells. The binding assay showed that many of the examined PBDEs have significant affinity to TR. Interestingly, some of these PBDEs, such as 4'-OH-BDE-17 and 2'-OH-BDE-28, acted as agonists in the reporter gene assay in MtT/E-2 cells, while they acted as antagonists in CHO cells. Our results demonstrated that whether PBDEs and their metabolites are TR agonists or antagonists depends on the cell type used in the assay, which may suggest that the thyroid hormone-disrupting actions of PBDEs differ among target tissues or species.