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Background: Mutations in TBL1X, part of the NCOR1/SMRT corepressor complex, were identified in patients with hereditary X-linked central congenital hypothyroidism and associated hearing loss. The role of TBL1X in thyroid hormone (TH) action, however, is incompletely understood. The aim of the present study was to investigate the role of TBL1X on T3-regulated gene expression in two human liver cell models. Methods: A human hepatoma cell line (HepG2) wherein TBL1X was downregulated using siRNAs, and human-induced pluripotent stem cell-derived hepatocytes (iHeps) generated from individuals with a TBL1X N365Y mutation. Both cell types were treated with increasing concentrations of T3. The expression of T3-regulated genes was measured by qPCR. Results: KLF9, CPT1A, and PCK1 mRNA expression were higher upon T3 stimulation in the HepG2 cells with decreased TBL1X expression compared to controls, while DIO1 mRNA expression was lower. Hemizygous TBL1X N365Y iHeps exhibited decreased expression of CPT1A, G6PC1, PCK1, FBP1, and ELOVL2 compared to cells with the heterozygous TBL1X N365Y allele, but KLF9 and HMGCS2 expression was unaltered. Conclusion: Downregulation of TBL1X in HepG2 cells and the TBL1X N365Y variant in iHeps have differential effects on T3-regulated gene expression. This suggests that TBL1X may play a gene context role in TH action.

Abstract Crosstalk between peripheral metabolic organs and the central nervous system is essential for body weight control. At the base of the hypothalamus, β-tanycytes surround the portal capillaries and function as gatekeepers to facilitate transfer of substances from the circulation into the cerebrospinal fluid and vice versa. Here, we investigated the role of the neuroplasticity gene doublecortin-like (DCL), highly expressed by β-tanycytes, in body weight control and whole-body energy metabolism. We demonstrated that DCL-knockdown through a doxycycline-inducible shRNA expression system prevents body weight gain by reducing adiposity in mice. DCL-knockdown slightly increased whole-body energy expenditure possibly as a result of elevated circulating thyroid hormones. In white adipose tissue (WAT) triglyceride uptake was increased while the average adipocyte cell size was reduced. At histological level we observed clear signs of browning, and thus increased thermogenesis in WAT. We found no indications for stimulated thermogenesis in brown adipose tissue (BAT). Altogether, we demonstrate an important, though subtle, role of tanycytic DCL in body weight control through regulation of energy expenditure, and specifically WAT browning. Elucidating mechanisms underlying the role of DCL in regulating brain-peripheral crosstalk further might identify new treatment targets for obesity.

Abstract Decades after World War II, major commemorations are still organised to collectively remember this war. Aiming for inclusive societies, the perspectives of immigrants with different war experiences are important to be heard in relation to these commemorations. Research reveals that commemorations can kindle difficult emotions such as sadness and bring distressing memories to the fore. Concurrently, psychosocial factors such as societal support and meaning making may buffer the emotional distress and contribute to a beneficial impact. It is not well known how this applies to immigrants. The present study explores how war-affected immigrants in the Netherlands relate to the Dutch Remembrance Day. Semi-structured interviews were conducted with 25 war-affected immigrants from 8 different countries (including countries in Europe, Asia, Africa, and South America). Qualitative analyses revealed that participants experienced multiple and mixed emotions during the Dutch Remembrance Day, including sadness, longing, and gratitude. Memories about own war experiences and losses often arose, of which the impact varied from distress to relief. The context of war in participants’ countries of origin, such as ongoing conflict or a contested history, often hindered commemoration of these wars. Through the Dutch commemoration, most war-affected immigrants experienced social connectedness and openness for (emotional) expression which contributed to dealing with their past experiences. Insights from this study may guide counsellors working with war-affected immigrants and help societies to organise optimally appealing commemorations within an inclusive society.

Background: Subclinical thyroid diseases are often the subject of debate concerning their clinical significance, the appropriateness of diagnostic testing, and possible treatment. This systematic review addresses the variation in international guidelines for subclinical hyperthyroidism, focusing on diagnostic workup, treatment, and follow-up recommendations. Methods: Following the PRISMA guidelines, we searched PubMed, Embase, and guideline-specific databases and included clinical practice guidelines with recommendations on subclinical hyperthyroidism. Guideline recommendations were extracted, and quality assessment was performed using selected questions of the Appraisal of Guidelines for Research & Evaluation (AGREE) II instrument. Results: Of the 2624 records screened, 22 guidelines were included, which were published between 2007 and 2021. Guideline quality was generally intermediate to low. Diagnostic approaches differed substantially, particularly in the extent of recommended testing. Treatment initiation depended on TSH levels, age, and comorbidities, but the level of detail regarding defining precise comorbidities varied. Recommendations for monitoring intervals for follow-up ranged from 3 to 12 months. Conclusion: This review underscores the existing variability in (inter)national guidelines concerning subclinical hyperthyroidism. There is a need for clear recommendations in guidelines considering diagnostic workup, treatment, and follow-up of subclinical hyperthyroidism. In order to establish this, future research should focus on determining clear and evidence-based intervention thresholds.

Abstract Background With this study, we aimed to explore the emotional experiences of sick-listed employees facing imminent job loss, as this emotional distress may hinder successful job search outcomes. The study had two objectives: (1) to develop and validate the Imminent Job Loss Scale (IJLS) for assessing pre-job loss grief reactions and (2) to examine its relationship to work attachment. Methods Development of the 9-item IJLS was carried out using feedback from an expert panel, consisting of five academic experts in grief and labour, five re-integration specialists, and five sick-listed employees facing imminent job loss. The psychometric properties of the IJLS were evaluated, and its association with work attachment was examined using data from 200 sick-listed employees facing imminent job loss. Results The IJLS demonstrated strong internal consistency and temporal stability, distinctiveness from depression and anxiety symptoms, and solid convergent validity. Work-centrality and organizational commitment were positively related to pre-job loss grief reactions, while work engagement and calling showed no significant associations. Conclusion This study provides valuable insights into pre-job loss grief reactions and shows the potential utility of the IJLS for screening and monitoring purposes. Understanding pre-job loss grief reactions can improve the re-integration and job prospects of sick-listed employees. In future research, explorations of these dynamics should continue to provide better support to sick-listed employees during this challenging period.

Background: Perceiving that society disregards grief after pregnancy loss (disenfranchised grief) elevates bereaved parents’ psychological burden.Objective: In this research, we aimed to compare the disenfranchisement of pregnancy loss with four other loss types considering the bereaved’s gender.Method: We collected data from Turkish participants (N = 1,280) using a 5 (loss type) x 2 (gender) between-subjects design with randomly assigned vignettes. Participants reported their expected grief and behavioural tendencies toward the bereaved. We conducted MANOVA and ANOVA analyses.Results: Results revealed that participants expected higher grief for pregnancy loss than two other disenfranchised grief types (former colleague’s death, grandfather’s diagnosis with Alzheimer’s). Expected grief for pregnancy loss was higher than or similar to the level for the best friend’s loss across examinations but lower than the level for the one-year-old child’s loss. Behaviour tendencies were alike across vignettes, and their results did not paint a coherent picture. Findings did not differ by the bereaved’s gender.Conclusion: Pregnancy loss might be less disenfranchised than bereaved parents perceive it, and parents’ perceptions could be targeted in therapeutic interventions.

Grief is highly prevalent in adolescents, however, there have been no studies investigating internet delivered cognitive behaviour therapy for grief in adolescents (ICBT-G-A). In this paper, the co-design of an unguided ICBT-G-A intervention is described, and a protocol outlined for a pilot randomised controlled trial of the intervention. Participants will be randomised to the intervention (delivered via eight modules over a four-week period) or a four-week waitlist control. Intervention participants will complete a follow-up assessment at one-month post-intervention (eight weeks from the pre-intervention assessment). The intervention outcomes assessed at pre-intervention, post-intervention and follow-up include wellbeing and symptoms of anxiety, depression, post-traumatic stress, and prolonged grief. User feedback on experiences and acceptability of the intervention will be sought and feasibility assessed via programmatic data on recruitment and attrition.

Background: Prolonged Grief Disorder (PGD) has recently been included in both the ICD-11 and DSM-5-TR diagnostic manuals. Studying its prevalence and correlates across cultures is vital for more effective identification, treatment, and prevention.Objective: This study aimed to examine prevalence rates of ICD-11-based PGD, in a representative Slovakian sample in response to deaths of loved ones occurring during the previous year. Further aims were to examine the factor structure of PGD symptoms and correlates of summed PGD item scores and PGD ‘caseness’.Method: Self-reported data on PGD, depression, anxiety, alcohol use, and descriptive characteristics were gathered from a representative sample of the Slovak population (N = 319).Results: Data were gathered from N = 1853 people; 319 participants (17.2%) reported a loss in the past year. The prevalence of probable PGD among these bereaved participants was 1.99% for recent losses (

Background: Police officers encounter various potentially traumatic events (PTEs) and may be compelled to engage in actions that contradict their moral codes. Consequently, they are at risk to develop symptoms of Posttraumatic Stress Disorder (PTSD), but also moral stress or moral injury (MI). To date, MI in police officers has received limited attention.Objective: The present study sought to identify classes of MI appraisals and PTSD symptoms among police officers exposed to PTEs, while also investigating potential clinical differences between these classes.Method: For this study, 421 trauma-exposed police officers were assessed on demographics and several clinical measurements including MI appraisals (self-directed and other-directed), PTSD severity, and general psychopathology. Latent class and regression analyses were conducted to examine the presence of different classes among trauma-exposed police officers and class differentiation in terms of demographics, general psychopathology, PTSD severity, mistrust, guilt, self-punishment, and feelings of worthlessness.Results: The following five classes were identified: (1) a ‘Low MI, high PTSD class’ (28%), (2) a ‘High MI, low PTSD class’ (11%), (3) a ‘High MI, high PTSD class’ (17%), (4) a ‘Low MI, low PTSD class’ (16%), and (5) a ‘High MI-other, high PTSD class’ (27%). There were significant differences between the classes in terms of age, general psychopathology, PTSD severity, mistrust, guilt, and self-punishment but no differences for gender and feelings of worthlessness.Conclusion: In conclusion, we identified five classes, each exhibiting unique patterns of cognitive MI appraisals and PTSD symptoms. This underscores the criticality of measuring and identifying MI in this particular group, as it allows for tailored treatment interventions.

ABSTRACTBackground: Refugees often suffer from trauma-related psychopathology, specifically posttraumatic stress disorder (PTSD). Negative world assumptions are strongly correlated with the development, course, and severity of PTSD.Objective: This study aimed to investigate whether there are distinct profiles of PTSD and negative world assumptions (NWA) and examine whether trauma load, torture, and gender differentially predict such symptom profiles.Method: In a sample of 225 treatment-seeking refugees who had resettled in the Netherlands, latent profile analysis was used to identify subgroups of patients sharing the same profile of PTSD and NWA symptoms. Predictors of profile membership were analyzed via multinomial logistic regression.Results: A three-profile solution yielded the best model fit: a low PTSD/low NWA profile (23.6%), a high PTSD/high NWA profile (41.8%), and a high PTSD/low NWA profile (34.7%). Participants who reported a higher trauma load, were more likely to be part of the high PTSD/high NWA profile or the high PTSD/low NWA profile in comparison to low PTSD/low NWA profile. Participants who reported having experienced torture were more likely to be part of the high PTSD/high NWA profile in comparison to low PTSD/low NWA profile. Gender did not differentiate between the profiles.Conclusions: This study reveals that among treatment-seeking refugees resettled in the Netherlands, there are distinct profiles of PTSD and NWA. These profiles indicate that PTSD and NWA are not uniformly experienced among refugees, emphasizing the diversity in their psychological responses to trauma. Among individuals experiencing severe PTSD symptoms, a subgroup was identified of individuals who additionally exhibited negative assumptions about themselves, others, and the world. Recognizing this heterogeneity is crucial in both research and clinical practice, particularly in the context of refugee mental health. Directions for future research are discussed.

Objective: Loss of function mutations in the insulin receptor substrate 4 (IRS4) gene cause a rare form of X-linked congenital central hypothyroidism in boys and men. Affected individuals show decreased thyroid-stimulating hormone (TSH) secretion. Members of the IRS family canonically act as scaffold proteins between tyrosine kinase receptors and downstream effectors. How loss of IRS4 affects TSH synthesis or secretion is unresolved. We therefore assessed IRS4’s role in the hypothalamic–pituitary–thyroid axis of Irs4 knockout mice. Methods: We generated two global Irs4 knockout mouse lines harboring either two or four base-pair deletions that result in frameshifts and loss of most of the IRS4 protein. Results: Under normal laboratory conditions, Irs4 knockout males did not exhibit impairments in pituitary expression of TSH subunit genes (Tshb or Cga) or in the thyrotropin-releasing hormone (TRH) receptor. Additionally, their serum thyroid hormone, triiodothyronine (T3) and thyroxine (T4), and hypothalamic Trh expression levels were normal. When Irs4 knockouts were rendered hypothyroid with a low-iodine diet supplemented with propylthiouracil for 3 weeks, their serum TSH increased similarly to wild-type males. Conclusion: Overall, Irs4 knockout mice do not exhibit central hypothyroidism or otherwise appear to phenocopy IRS4 deficient patients. Compensation by another IRS protein may explain euthyroidism in these animals.

Abstract Background The COVID-19 pandemic and accompanying societal measures have impacted children and their families all over the world. Little is known about the factors associated with mental health outcomes in young children (i.e., 1 to 6 years old) during the pandemic. The current study aimed to examine associations with potential risk and protective factors, i.e., direct COVID-19 exposure factors as well as within-family characteristics. Methods Caregivers of children aged 1–6 years old were recruited in the Netherlands to participate in an ongoing longitudinal research project. In the current study, baseline data—collected during the 1st year of the pandemic—are reported. The final sample consisted of 2762 caregivers who answered questionnaires assessing negative and positive dimensions of their children’s mental health (i.e., anxiety, depressive symptoms, anger, sleep problems, positive affect, and self-regulation). Furthermore, caregivers provided information regarding: (1) Direct COVID-19 related factors, i.e., parental infection and death of a family member or close friend due to COVID-19, (2) Family related COVID-19 factors, i.e., parental perceived impact of the pandemic and COVID-19 related parent–child emotion regulation strategies (i.e., active, avoidant and information-focused strategies), (3) General caregiver’s distress, i.e., parental mental health, parental feelings of rejection towards their child. Regression analyses were used to examine associations with children’s mental health. Results Direct COVID-19 related factors were not associated with more mental health problems in the children, though parental COVID-19 infections were related with less anger in children. Family related COVID-19 factors and caregiver’s distress were related with children’s mental health. Higher parental perceived negative impact of the pandemic, lower parental perceived positive impact of the pandemic, more avoidant as well as more active and information-focused parent–child emotion regulation strategies, more caregiver’s mental health problems and more parental feelings of rejection towards their child were related with more mental health problems in the child. Conclusion Direct exposure to COVID-19 was not related with more mental health problems in the child. Family related COVID-19 factors and caregiver’s distress appear to play a more important role for young children’s mental health. Findings may inform prevention and intervention programs for potential future global crises as well as other stressful events.

Mobile health (mHealth) apps have been shown to be useful to monitor and reduce mental health problems across a variety of stress-related and affective disorders, yet research on the value of apps for prolonged grief is scarce. Therefore, the main aim of this study was to elucidate bereaved parents' experiences of using the self-help app My Grief with a focus on helpfulness, satisfaction, and usability. Data were derived from closed-ended and open-ended questions administered at the 3-month post-assessment of the intervention group (n = 67) within a randomized controlled trial testing the effects of access to the My Grief app. The sample consisted of 88 % women, with a mean age of 47 years, who predominantly lost their child to cancer (41 %), on average 4.8 years ago. Participating parents indicated that the My Grief app helped them increase their knowledge about prolonged grief and track their grief over time. The app was experienced as easy to navigate and around half of the parents used the app more than one day a week. Almost all parents were satisfied with the app and would recommend it to other parents in similar situations. The findings add to the knowledge base justifying mHealth within support systems for bereaved adults.

Objective: Congenital hypothyroidism (CH) is an inborn thyroid hormone (TH) deficiency mostly caused by thyroidal (primary CH) or hypothalamic/pituitary (central CH) disturbances. Most CH newborn screening (NBS) programs are thyroid-stimulating-hormone (TSH) based, thereby only detecting primary CH. The Dutch NBS is based on measuring total thyroxine (T4) from dried blood spots, aiming to detect primary and central CH at the cost of more false-positive referrals (FPRs) (positive predictive value (PPV) of 21% in 2007–2017). An artificial PPV of 26% was yielded when using a machine learning-based model on the adjusted dataset described based on the Dutch CH NBS. Recently, amino acids (AAs) and acylcarnitines (ACs) have been shown to be associated with TH concentration. We therefore aimed to investigate whether AAs and ACs measured during NBS can contribute to better performance of the CH screening in the Netherlands by using a revised machine learning-based model. Methods: Dutch NBS data between 2007 and 2017 (CH screening results, AAs and ACs) from 1079 FPRs, 515 newborns with primary (431) and central CH (84) and data from 1842 healthy controls were used. A random forest model including these data was developed. Results: The random forest model with an artificial sensitivity of 100% yielded a PPV of 48% and AUROC of 0.99. Besides T4 and TSH, tyrosine, and succinylacetone were the main parameters contributing to the model’s performance. Conclusions: The PPV improved significantly (26–48%) by adding several AAs and ACs to our machine learning-based model, suggesting that adding these parameters benefits the current algorithm.

Objective: International guidelines concerning subclinical hyperthyroidism and thyroid cancer advice absolute cut-off values for aiding clinical decisi ons in the low range of thyroid-stimulating hormone (TSH) concentrations. As TSH assays are known to be poorly standardized in the normal to high range, we performed a TSH assay method comparison focusing on the low range. Methods: Sixty samples, selected to cover a wide range of TSH concentrat ions (

Transducin β-like 1 X-linked receptor 1 (TBL1XR1) is a WD40 repeat-containing protein and part of the corepressor complex SMRT/NCoR that binds to the thyroid hormone receptor (TR). We recently described a mutation in TBL1XR1 in patients with Pierpont syndrome. A mouse model bearing this Tbl1xr1 mutation (Tbl1xr1Y446C/Y446C) displays several aspects of the Pierpont phenotype. Although serum thyroid hormone (TH) concentrations were unremarkable in these mice, tissue TH action might be affected due to the role of TBL1XR1 in the SMRT/NCoR corepressor complex. The aim of the present study was to evaluate tissue TH metabolism and action in a variety of tissues of Tbl1xr1Y446C/Y446C mice. We studied the expression of genes involved in TH metabolism and action in tissues of naïve Tbl1xr1Y446C/Y446C mice and wild type (WT) mice. In addition, we measured deiodinase activity in liver (Dio1 and Dio3), kidney (Dio1 and Dio3) and BAT (Dio2). No striking differences were observed in the liver, hypothalamus, muscle and BAT between Tbl1xr1Y446C/Y446C and WT mice. Pituitary TRα1 mRNA expression was lower in Tbl1xr1Y446C/Y446C mice compared to WT, while the mRNA expression of Tshβ and the positively T3-regulated gene Nmb were significantly increased in mutant mice. Interestingly, Mct8 expression was markedly higher in WAT and kidney of mutants, resulting in (subtle) changes in T3-regulated gene expression in both WAT and kidney. In conclusion, mice harboring a mutation in TBL1XR1 display minor changes in cellular TH metabolism and action. TH transport via MCT8 might be affected as the expression is increased in WAT and kidney. The mechanisms involved need to be clarified.

Thyroid hormone (TH) is indispensable for brain development in utero and during the first 2–3 years of life, and the negative effects of TH deficiency on brain development are irreversible. Detection of TH deficiency early in life by neonat al screening allows early treatment, thereby preventing brain damage. Inborn shortage of TH, also named congenital hypothyroidism (CH), can be the result of defective thyroid gland development or TH synthesis (primary or thyroidal CH (CH-T)). Primary CH is characterized by low blood TH and elevated thyroi d-stimulating hormone (TSH) concentrations. Less frequently, CH is due to insufficient stimulation of the thyroid gland because of disturbed hypothalamic or pituitary function (central CH). Central CH is characterized by low TH concentrations, while TSH is normal, lo w or slightly elevated. Most newborn screening (NBS) programs for CH are primarily TSH based and thereby do not detect central CH. Only a few NBS programs worldwide aim to detect both forms of CH by different strategies. In the Netherlands, we have a uni que T4–TSH–thyroxine-binding globulin (TBG) NBS algorithm for CH, which enables the detection of primary and central CH. Although the necessity of central CH detection by NBS is still under debate, it has been shown that most central CH patients have moderate-to-severe hyp othyroidism instead of mild and that early detection of central CH by NBS probably improves its clinical outcome and clinical care for central CH patients with multiple pituitary hormone deficiency. We are therefore convinced that detection of central CH by NBS is of utmost importance.

Most children confronted with the death of a loved one do not experience persisting psychological problems. However, for some, acute grief reactions develop into prolonged grief disorder (PGD) and other mental health problems. Research findings suggest that bereavement outcomes in children are associated with negative cognitions and avoidant coping and with different parenting behaviours. However, knowledge about factors influencing grief in children is still limited and few studies have examined the relative impact of psychological (individual-level) variables and systemic (family-level) variables in affecting their responses to loss. The aim of the current study was to examine the association of different bereavement outcomes in 8-18 year old children (including levels of self-rated PGD, depression, and posttraumatic stress (PTS)) with sociodemographic variables, individual-level variables (including negative cognitions and anxious and depressive avoidance), and family-level variables (including the severity of caregiver's PGD, depression, and anxiety, and indices of parenting behaviours, rated both by children and by their caregivers). Questionnaire data were used from 159 children plus one of their caregivers, gathered as part of the pre-treatment assessment in a randomized controlled trial. Results showed that most of the children's bereavement outcomes, including PGD severity and PTS severity, were associated with indices of negative cognitions and avoidance behaviours. Caregiver's depression and anxiety showed a very small, yet significant, association with two children's outcomes. Caregiver-rated reasoning/induction (one index of parenting behaviours) showed a small association with children's PTS-related functional impairment. Exploratory analyses indicated that the linkage between parenting behaviour and children's outcomes may be moderated by whether the behaviour comes from father or mother. This is one of the first studies examining how individual cognitive behavioural variables plus the mental health of caregivers and indices of parenting may affect PGD and other outcomes in bereaved children. The findings provide tentative indications that individual and family-level variables influence these outcomes, albeit that more research is urgently needed.

The death of a loved one may lead to posttraumatic stress disorder (PTSD). Although it is conceivable that unnatural losses (caused by e.g., accidents, homicide, or suicide) render people more vulnerable to PTSD than natural losses (e.g., caused by illnesses) this is an understudied issue. The current study sought to enhance knowledge about the presentation and prevalence of PTSD symptoms, in people confronted with natural, non-sudden and unnatural, sudden losses. Considering that PTSD is defined differently in DSM-5 and ICD-11, we compared PTSD severity and prevalence rates between these diagnostic systems. Self-reported data were available from a heterogeneous sample of 1064 bereaved people (Mage = 52.13 years, 86 % female). Confirmatory factor analyses supported the DSM-5-based and ICD-11-based symptom clustering. DSM-5 yielded higher prevalence rates of probable PTSD than ICD-11 criteria. PTSD cluster and total scores were significantly higher for participants confronted with unnatural losses than participants confronted with natural losses. Rates of probable PTSD (based on DSM-5 and ICD-11) were also higher in the former group. Confrontation with an unnatural loss was not associated with PTSD scores beyond other sociodemographic and loss-related variables considered. Results show that bereavement-related PTSD is assessed differently in DSM-5 and ICD-11. Cause of death affected PTSD but less strongly than anticipated.

Thyroid hormones play an essential role in regulating whole-body homeostasis. Deiodinases are known to convert thyroid hormone from the prohormone thyroxine (T4) to the bioactive hormone tri-iodothyronine (T3) and convert both T4 and T3 toward their inactive metabolites 3,3’,5’-tri-iodothyronine (rT3) and 3,3’-di-iodothyronine (3,3’- T2). Deiodinases are thus important for the regulation of intracellular thyroid hormone concentrations. This is known to be crucial both during development and adult life in regulating thyroid hormone-related gene transcription. This review discusses the importance of liver deiodinases in determining serum and liver thyroid hormone concentrations, liver metabolism and liver disease.

Introduction: In our hospital, physicians noticed high free thyroxine (fT4) concentrations without complete suppression of thyroid-stimulating hormone (TSH) in blood samplesof patients at the outpatient clinic, which appeared to occur more often following the introduction of a new fT4 immunoassay. This discordance may be explained by incorrect reference intervals, analytical issues, or patient-related factors. We aimed to establish the contribution of the possible factors involved. Methods: Reference intervals of both fT4 immunoassays were re-evaluated using blood samples of healthy volunteers and the new immunoassay’s performance was assessed using internal quality controls and external quality rounds. The frequency of discordant fT4 and TSH pairings obtained from laboratory requests were retrospectively analysed using a Delfia (n = 3174) and Cobas cohort (n = 3408). Last, a literature search assessed whether the time of blood draw and the time of levothyroxine (L-T4) ingestion may contribute to higher fT4 concentrations in L-T4 users. Results: The original reference intervals of both fT4 immunoassays were confirmed and no evidence for analytical problems was found. The Delfia (n = 176, 5.5%) and Cobas cohorts (n = 295, 8.7%) showed comparable frequencies of discordance. Interestingly, 72–81% of the discordant results belonged to L-T4 users. Literature indicated the time of blood withdrawal of L-T4 users and, therefore, the time of L-T4 intake as possible explanations. Conclusions: High fT4 without suppressed TSH concentrations can mainly be explained by L-T4 intake. Physicians and laboratory specialists should be aware of this phenomenon to avoid questioning the assay’s performance or unnecessarily adapting the L-T4 dose in patients.

In this study, we investigate the changes in the crystalline structure of MBE-deposited SrTiO3 layers on Si with different deviations from Sr/Ti stoichiometry as deposited but also after annealing at high temperatures (>600 °C). We show that as-grown 15 nm thick non-stochiometric SrTiO3 layers present surprisingly lower FWHM values of the (002) omega diffraction peak compared to fully stoichiometric layers of similar thickness. This can misleadingly point to superior crystalline quality of such non-stochiometric layers. However, thermal post-deposition anneals of these layers at temperatures up to 850 °C in oxygen show strong detrimental effects on the crystalline structure, surface and interface with the Si (001) substrate. On the contrary, the post-deposition anneals applied to the stoichiometric samples strongly improve the physical, optical and electrical properties of the epitaxial SrTiO3 thin films.

ABSTRACTBackground: With the release of the text revision of the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5-TR), criteria for Prolonged Grief Disorder (PGD) were included. This necessitates studying grief trajectories based on these criteria.Objective: This is the first study examining latent trajectories of DSM-5-TR-based PGD symptom levels and testing whether specific risk factors (e.g. cause of death) predicted PGD trajectories.Method: We evaluated latent DSM-5-TR PGD trajectories using pooled existing data collected at 6–12, 13–24, and 25–60 months post-loss in Danish and Dutch bereaved adults (N = 398). Latent Growth Mixture Modelling (LGMM) was employed to determine the trajectories. Multinomial logistic regression analyses were used to examine which risk factors predicted class membership.Results: The four-class LGMM solution with a quadratic term was best-fitting the data. This solution represented four trajectories: High stable PGD (6%), High PGD quick recovery (10%), High PGD slow recovery (35%), and Low PGD symptoms (49%). Participants with a higher educational level were more likely to be assigned to the Low PGD symptoms trajectory compared to High stable PGD and High PGD slow recovery trajectories. Unnatural causes of death increased the likelihood of being in the High stable PGD and High PGD slow recovery trajectories compared to the Low PGD symptoms trajectory.Conclusions: Consistent with prior research, the Low PGD symptoms trajectory was the most common. A significant minority experienced high and stable levels of PGD within five years after the loss. About one-third of participants experienced high acute grief levels that decreased slowly; how slow decreasing symptoms relate to an individual’s functioning requires further attention. This study demonstrates that a significant minority of bereaved people develop acute PGD symptomatology that does not diminish within five years post-loss, emphasizing the need for early screening for PGD to prevent long-lasting complaints.

Background: Around 10% of bereaved youths experience symptoms of prolonged grief disorder (PGD). Recently, PGD was included in the two main classification systems for mental disorders: the ICD-11 and DSM-5-TR. Assessing PGD symptoms in youth is currently hindered by the lack of instruments for ICD-11 and DSM-5-TR criteria. To fill this gap, we developed an instrument to assess PGD symptoms in children and adolescents, the Traumatic Grief Inventory – Kids – Clinician-Administered (TGI-K-CA), based on input of grief experts and bereaved children. Methods: Five experts rated the items on alignment with DSM-TR and ICD-11 PGD symptoms and comprehensibility. The adjusted items were then presented to seventeen bereaved youths (Mdnage = 13.0 years, range = 8–17 years). Using the Three-Step Test Interview (TSTI), children were asked to verbalize their thoughts while answering the items. Results: Issues raised by experts were mostly related to alignment with the DSM-5-TR/ICD-11 symptom, ambiguous formulation of the items, or low comprehensibility for children and adolescents. Items raising fundamental issues according to experts were adjusted. The TSTI showed that children encountered relatively few problems with the items. Frequently reported problems with some of the items (e.g. regarding comprehensibility) led to final adjustments. Conclusion: With input from grief experts and bereaved youths, an instrument to assess PGD symptoms as defined in DSM-5-TR and ICD-11 in bereaved youths was finalized. Further quantitative research is currently undertaken to evaluate the instrument’s psychometric qualities.

Objective: Thyroid hormone measurements are often performed in pregnant women, as hypo- and hyperthyroidism during pregnancy can severely affect t he fetus. Serum free thyroxine (fT4) measurements are well known for their analytical challenges, due to low serum concentrations and the subtle equilibrium between free and bound T4 (to thyroid-binding globulin (TBG), transthyretin and albumin). Pregnant wo men have high TBG concentrations due to an increase in human chorionic gonadotropin (hCG) and estrogen and lower albumin concentrations which change the equilibrium a nd may affect the validity of fT4 measurements in their samples. As accurate seru m fT4 measurements in pregnant women are important for the long-term health of the fetus, we aimed to evaluate the accuracy of several fT4 immunoassays in the serum of pregnant women. Methods: FT4 was measured in healthy controls and pregnant women using a candidate-reference method (LC-MS/MS) and five commercially available auto mated immunoassays (Alinity (Abbott), Atellica (Siemens), Cobas (Roche), Lumipulse (Fujirebio) and UniCel DXI (Beckman Coulter)). Method comparisons (Bland Altman plots and Passing and Bablok analyses) were performed. Results: Serum samples from both healthy controls (n = 30) and pregnant women (n = 30; mean gestational age, 24.8 weeks) were collected. The fT4 immun oassays deviated +7 to +29% more from the LC-MS/MS in serum samples of pregnant wom en than healthy controls (falsely high). Conclusions: Our results indicate that immunoassays overestimate fT4 in pregnant women, which might lead to an overestimation of thyroid status. Physicians and laboratory specialists should be aware of this phenomenon to avoid drawing false conclusions about thyroid function in pregnant women.