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BACKGROUND There is increasing evidence, in transgenic mice and in vitro, that inhibitory killer cell immunoglobulin-like receptors (iKIRs) can modulate T cell responses. Furthermore, we have previously shown that iKIRs are an important determinant of T cell–mediated control of chronic viral infection and that these results are consistent with an increase in the CD8+ T cell lifespan due to iKIR-ligand interactions. Here, we tested this prediction and investigated whether iKIRs affect T cell lifespan in humans in vivo.METHODS We used stable isotope labeling with deuterated water to quantify memory CD8+ T cell survival in healthy individuals and patients with chronic viral infections.RESULTS We showed that an individual’s iKIR-ligand genotype was a significant determinant of CD8+ T cell lifespan: in individuals with 2 iKIR-ligand gene pairs, memory CD8+ T cells survived, on average, for 125 days; in individuals with 4 iKIR-ligand gene pairs, the memory CD8+ T cell lifespan doubled to 250 days. Additionally, we showed that this survival advantage was independent of iKIR expression by the T cell of interest and, further, that the iKIR-ligand genotype altered the CD8+ and CD4+ T cell immune aging phenotype.CONCLUSIONS Together, these data reveal an unexpectedly large effect of iKIR genotype on T cell survival.FUNDING Wellcome Trust; Medical Research Council; EU Horizon 2020; EU FP7; Leukemia and Lymphoma Research; National Institute of Health Research (NIHR) Imperial Biomedical Research Centre; Imperial College Research Fellowship; National Institutes of Health; Jefferiss Trust.

IntroductionUnaccompanied refugee minors (URMs) are at increased risk of developing mental health problems, such as symptoms of posttraumatic stress disorder (PTSD) and depression. In addition, URMs face several barriers to mental health care. Few studies have evaluated trauma-focused interventions for URMs that target these issues. The current study evaluated a multimodal trauma-focused treatment approach for URMs. It aimed to provide an initial indication of the effectiveness of this treatment approach and to provide a qualitative evaluation assessing treatment satisfaction of the participating URMs.MethodsA mixed-methods study was conducted among ten URMs, combining quantitative data with qualitative data through triangulation. Quantitative data were collected using a non-concurrent multiple baseline design in which repeated, weekly assessments were carried out during a randomized baseline period, during treatment, and during a 4-week follow-up period. Questionnaires assessing PTSD (Children’s Revised Impact of Event Scale) and symptoms of depression (The Patient Health Questionnaire-9, modified for adolescents) were used. In addition, treatment satisfaction was measured post-treatment using a semi-structured interview.ResultsDuring the qualitative evaluation, all but one URM noted they found the trauma-focused treatment approach useful and felt the treatment had positively impacted their wellbeing. However, the results of the quantitative evaluation did not show clinically reliable symptom reductions at posttest or follow-up. Implications for clinical practice and research are discussed.DiscussionThe current study presents our search in developing a treatment approach for URMs. It adds to the current knowledge about methodological considerations in evaluating treatments for URMs, the potential effects of trauma-focused treatments on URMs, and the implementation of treatments for URMs.Clinical trial registration: The study was registered in the Netherlands Trial Register (NL8519), 10 April 2020.

Innate immune cells, including macrophages, are functionally affected by thyroid hormone (TH). Macrophages can undergo phenotypical alterations, shifting between proinflammatory (M1) and immunomodulatory (M2) profiles. Cellular TH concentrations are, among others, determined by TH transporters. To study the effect of TH and TH transporters on macrophage polarization, specific proinflammatory and immunomodulatory markers were analyzed in bone marrow-derived macrophages (BMDMs) depleted of triiodothyronine (T3) and BMDMs with a knockout (KO) of Mct8 and Mct10 and a double KO (dKO) of Mct10/Mct8. Our findings show that T3 is important for M1 polarization, while a lack of T3 stimulates M2 polarization. Mct8 KO BMDMs are unaffected in their T3 responsiveness, but exhibit slight alterations in M2 polarization, while Mct10 KO BMDMs show reduced T3 responsiveness, but unaltered polarization markers. KO of both the Mct8 and Mct10 transporters decreased T3 availability and, contrary to the T3-depleted BMDMs, showed partially increased M1 markers and unaltered M2 markers. These data suggest a role for TH transporters besides transport of TH in BMDMs. This study highlights the complex role of TH transporters in macrophages and provides a new angle on the interaction between the endocrine and immune systems.

Background: The coronavirus disease 2019 (COVID-19) pandemic is associated with an increase in mortality rates globally. Given the high numbers of deaths and the potentially traumatic characteristics of COVID-19 deaths, it is expected that grief-related distress levels are higher in COVID-19 bereaved (compared to non-COVID-19 bereaved) people. This living systematic review (LSR) investigates the empirical evidence regarding this claim. More specifically, this LSR summarizes studies evaluating prevalence and correlates of positive and negative psychological effects of COVID-19 bereavement. This iteration synthesizes evidence up to July 2022. Methods: Systematic searches were conducted in PsychInfo, Web of Science, and Medline by two independent reviewers. Eligible studies included quantitative peer-reviewed articles reporting on positive and/or negative psychological outcomes, using validated measures, in COVID-19 bereaved adults. The primary outcome was prolonged grief symptoms (PG). Results: Searches identified 9871 articles, whereof 12 studies met the inclusion criteria. All studies included prevalence rates and/or symptom-levels of psychological outcomes after COVID-19 losses. Prevalence rates of psychological outcomes were primarily reported in terms of (acute) PG, pandemic grief, depression, anxiety, and functional impairment, and varied widely between studies (e.g., ranged between 29% and 49% for acute PG). No studies reported on prevalence rates of positive psychological outcomes. Closer kinship to the deceased, death unexpectedness, and COVID-19 stressors were identified as correlates of increased psychological symptoms. Conclusions: Due to the small number and heterogeneity of studies, knowledge about psychological effects of COVID-19 bereavement is limited. This LSR offers a regular synthesis of up-to-date research evidence to guide clinicians, policy makers, public health professionals, and future research on the psychological effects of COVID-19 bereavement.

Abstract Background A key feature of anorexia nervosa is body image disturbances and is often expressed by dysfunctional body-related behaviours such as body checking and body avoiding. These behaviours are thought to contribute to both the maintenance and relapse of AN, yet empirical evidence is scarce. One variable that may contribute to the need for engaging in these behaviours is intolerance of uncertainty. This study aims to investigate body checking and body avoiding and its relations with intolerance of uncertainty in women with anorexia nervosa (AN-ill; 70), women recovered from AN (AN-rec; 85) and control group (127). Methods Three questionnaires were completed, measuring eating pathology, intolerance of uncertainty and body checking and body avoiding. One-way ANOVAS were used to test group differences. Moderation analyses were used to investigate associations between variables. Results Levels of intolerance of uncertainty, body checking and body avoiding were highest in AN-ill followed by AN-rec and, lastly, the control group, confirming group differences. Intolerance of uncertainty was associated with body checking in the AN-rec group and the control group but not in the AN-ill group. The association between intolerance of uncertainty and body avoiding was reported in the AN-rec group and only marginally in the control group. Conclusion Levels of intolerance of uncertainty, body checking and body avoiding were highest in AN-ill, however still elevated in AN-rec, confirming the presence of body image disturbances, even after recovery. The unique associations between intolerance of uncertainty and body checking and body avoiding within the studied groups may represent different stages of the illness. In the AN-rec group, the relation between intolerance of uncertainty, body checking and body avoiding may be driven by trait anxiety. For AN-ill group, body checking and body avoiding may eventually have grown into habitual patterns, rather than a strategy to ameliorate anxiety and uncertainty. Plain English summary Women with anorexia nervosa often experience disturbances in their body image and are expressed in body-related behaviours such as body checking and body avoiding. These behaviours are thought to contribute to both the maintenance and relapse of anorexia nervosa. Intolerance of uncertainty is defined as the incapacity to tolerate uncertainty and may contribute to the need for engaging in these behaviours. This study aims to investigate body checking and body avoiding and its relations with intolerance of uncertainty in women with anorexia nervosa (AN-ill; 70), women recovered from AN (AN-rec; 85) and control group (127). Three questionnaires were completed, measuring eating pathology, intolerance of uncertainty and body checking and body avoiding. Levels of intolerance of uncertainty, body checking and body avoiding were highest in AN-ill and still elevated in AN-rec, even after recovery. The associations between intolerance of uncertainty and body checking and body avoiding within the studied groups may represent different stages of the illness. In the AN-rec group, the relation between intolerance of uncertainty, body checking and body avoiding may be driven by trait anxiety. For AN-ill group, body checking and body avoiding may have grown into habitual patterns, rather than a strategy to ameliorate anxiety and uncertainty.

Abstract Background There is a lack of existing research on grief following the intentional death of people suffering from a mental disorder. Our study aims to provide insight into grief experiences and social reactions of bereaved persons who lost their life partners, who were suffering from a mental disorder, to physician-assisted dying (PAD) or suicide. Methods For this mixed-methods research, we conducted a survey and in-depth interviews with 27 persons living in the Netherlands and bereaved by the death of their life partners. The deceased life partners suffered from a mental disorder and had died by physician-assisted dying (n = 12) or suicide (n = 15). Interviews explored grief experiences and social reactions. In the survey we compared self-reported grief reactions of partners bereaved by suicide and PAD using the Grief Experience Questionnaire. Results Compared to suicide, physician-assisted dying was associated with less severe grief experiences of the bereaved partners. Participants reported that others rarely understood the suffering of their deceased partners and sometimes expected them to justify their partners’ death. Following physician-assisted dying, the fact that the partner’s euthanasia request was granted, helped others understand that the deceased person’s mental suffering had been unbearable and irremediable. Whereas, following suicide, the involvement of the bereaved partners was sometimes the focus of judicial inquiry, especially, if the partner had been present during the death. Conclusion When individuals suffering from a mental disorder die by suicide or PAD, their bereaved partners may experience a lack of understanding from others. Although both ways of dying are considered unnatural, their implications for bereaved partners vary considerably. We propose looking beyond the dichotomy of PAD versus suicide when studying grief following the intentional death of people suffering from a mental disorder, and considering other important aspects, such as expectedness of the death, suffering during it, and partners’ presence during the death.

Background and objectives: A rise in prolonged grief disorder (PGD) levels was expected due to COVID-19 deaths. We tested this assumption, by comparing PGD-severity among people who experienced a death of a loved one during the pandemic caused by a natural (e.g., illness), COVID-19, or unnatural (e.g., accidents, suicides, homicides) loss on average 8 months earlier and in a subgroup of people bereaved ≥12 months earlier. Design and methods: Self-rated DSM-5-TR (acute) PGD levels (using the Traumatic Grief Inventory-Self Report plus) were compared among Dutch adults who experienced a natural (N = 1036), COVID-19 (N = 76), or unnatural loss (N = 271) during the pandemic. Analyses of covariance were used. Results: About two-thirds of the participants scored above the cut-off for (acute) probable PGD. Significantly higher acute PGD-severity was found in people after unnatural loss compared with COVID-19 (B = -2.44 (SE=0.87), p = .005) or natural loss (B = -1.78 (SE=0.45), p

Steroid hormone levels of patients may be monitored via dried blood spot (DBS) sampling at home. Stability of steroid hormones in DBS samples, however, needs to be established. DBS samples from healthy volunteers were collected and stored at various temperatures. Steroid hormone concentrations in DBS were measured directly, at day 2, day 7 and day 14 following storage at 37 °C and after 7 days, 14 days, 3 months and 6 months following storage at −20 °C, 4 °C and room temperature (RT). Cortisol, cortisone, corticosterone, testosterone, androstenedione, and 17-hydroxyprogesterone (17-OHP) were assessed using LC-MS/MS. All steroids were stable (±15 %) up to 14 days when stored at 37 °C, except for cortisone (only stable until 2 days). All steroids were stable up to 6 months when stored at −20 °C, 4 °C and RT. However, there were some exceptions, for androstenedione at RT (only stable until 7 days), for 17-OHP when stored at −20 °C (only stable until 3 months), for cortisone at RT and 4 °C (only stable until 14 days), and cortisol at RT (only stable until 3 months). Overall, we demonstrated stability of steroid hormone concentrations in DBS under various conditions which may be encountered during shipping to the diagnostic laboratory and during long-term storage before analysis. [ABSTRACT FROM AUTHOR]

Objective: The Traumatic Grief Inventory‐Self Report Plus (TGI‐SR+) measures the most recent prolonged grief disorder (PGD) symptom sets defined in the 11th edition of the International Statistical of Diseases and Related Health Problems (ICD‐11) and the text revision of the fifth edition of the Diagnostical and Statistical Manual of Mental Disorders (DSM‐5‐TR). However, the TGI‐SR+ has not yet been translated and validated in Chinese. This study aims to evaluate the psychometric properties of the Chinese translation of the TGI‐SR+. Methods: We examined the Chinese TGI‐SR+'s factor structure, internal consistency, convergent validity, discriminant validity, known‐groups validity, and optimal clinical cut‐off scores in 443 Chinese bereaved adults. Results: Confirmatory factor analyses showed that the two‐factor models showed the best fit for the Chinese TGI‐SR+ items assessing ICD‐11 and DSM‐5‐TR prolonged grief symptoms. Items assessing ICD‐11 and DSM‐5‐TR prolonged grief symptoms demonstrated good internal consistency. Associations of TGI‐SR+ scores with symptom levels of prolonged grief (assessed by the International Prolonged Grief Disorder Scale), posttraumatic stress, anxiety, and depression supported convergent and discriminant validity. Associations with background/loss‐related variables provided evidence for known‐groups validity. Cut‐off points for probable ICD‐11 PGD (liberal scoring rule), probable ICD‐11 PGD (conservative scoring rule), and probable DSM‐5‐TR PGD were ≥67, ≥75, and ≥68, respectively. Discussion: The Chinese TGI‐SR+ appears to be a reliable and valid measure to assess prolonged grief symptoms per ICD‐11 and DSM‐5‐TR among Chinese bereaved adults. [ABSTRACT FROM AUTHOR]

Most studies examining prolonged grief disorder (PGD) in people bereaved during the COVID‐19 pandemic are focused on psychopathology. However, mental health encompasses both absence of psychopathology and presence of well‐being. This is the first study examining symptom profiles of early PGD and subjective mental well‐being in 266 Dutch adults recently bereaved during the pandemic. Early PGD and well‐being indicators were assessed with the Traumatic Grief Inventory–Self Report Plus and the World Health Organization–Five Well‐Being Index, respectively. Latent class analysis identified four classes: low PGD/high well‐being (32%), low PGD/moderate well‐being (24%), moderate PGD/high well‐being (23%) and high PGD/low well‐being class (21%). People in the poorer mental health classes were more likely to be female, lower educated, suffering from a mental disorder, have a poor health status, closer kinship to the deceased, and higher risk of severe COVID‐19. Classifying adults according to symptom profiles of negative and positive outcomes provides a more complete picture of mental health in bereaved people and offers potential intervention targets. [ABSTRACT FROM AUTHOR]

Introduction: The decision to terminate a pregnancy due to fetal anomalies can have a significant emotional impact, especially in second‐trimester terminations. Previous studies on the psychological consequences of pregnancy termination have had limitations, and little is known about the outcomes for partners and the impact of fetal donation. Therefore, we aimed to investigate the psychological effects of second‐trimester pregnancy termination and identify factors associated with outcomes in both women and men, including donation of fetal remains to science. Material and Methods: A longitudinal cohort study was conducted at the Amsterdam UMC in the Netherlands, involving women and partners who underwent termination at or before 23 weeks and 6 days of gestation. Questionnaires were administered at termination, 6 weeks, and 4 months after. We utilized validated questionnaires to assess psychological morbidity (grief, post‐traumatic stress and postnatal depression and quality of life [QoL]), and factors that could potentially influence outcomes. Results: Of 241 participants, women displayed more pronounced psychological distress than men, though both groups improved over time. Four months after termination, 27.4% of women and 9.1% of men showed signs of pathological grief. Scores indicative for postnatal depression occurred in 19.8% women and 4.1% of men. A prior psychiatric history was a consistent predictor of poorer outcomes. Fetal donation to the Dutch Fetal Biobank was associated with reduced likelihood of symptoms of complicated grief four months after termination. Conclusions: Second‐trimester termination of pregnancy for fetal anomalies can lead to psychological morbidity, particularly in women. However, there is a notable improvement over time for both groups. Individuals with prior psychiatric history appear more vulnerable post‐termination. Also, fetal donation to science did not have a negative impact on psychological well‐being. [ABSTRACT FROM AUTHOR]

BACKGROUND. There is increasing evidence, in transgenic mice and in vitro, that inhibitory killer cell immunoglobulin-like receptors (iKIRs) can modulate T cell responses. Furthermore, we have previously shown that iKIRs are an important determinant of T cell-mediated control of chronic viral infection and that these results are consistent with an increase in the [CD8.sup.+] T cell lifespan due to iKIR-ligand interactions. Here, we tested this prediction and investigated whether iKIRs affect T cell lifespan in humans in vivo. METHODS. We used stable isotope labeling with deuterated water to quantify memory [CD8.sup.+] T cell survival in healthy individuals and patients with chronic viral infections. RESULTS. We showed that an individual's iKIR-ligand genotype was a significant determinant of [CD8.sup.+] T cell lifespan: in individuals with 2 iKIR-ligand gene pairs, memory [CD8.sup.+] T cells survived, on average, for 125 days; in individuals with 4 iKIR-ligand gene pairs, the memory [CD8.sup.+] T cell lifespan doubled to 250 days. Additionally, we showed that this survival advantage was independent of iKIR expression by the T cell of interest and, further, that the iKIR-ligand genotype altered the [CD8.sup.+] and [CD4.sup.+] T cell immune aging phenotype. CONCLUSIONS. Together, these data reveal an unexpectedly large effect of iKIR genotype on T cell survival. FUNDING. Wellcome Trust; Medical Research Council; EU Horizon 2020; EU FP7; Leukemia and Lymphoma Research; National Institute of Health Research (NIHR) Imperial Biomedical Research Centre; Imperial College Research Fellowship; National Institutes of Health; Jefferiss Trust., Introduction The human killer cell immunoglobulin-like receptors (KIRs) are a family of inhibitory and activating receptors. They are expressed predominantly by NK cells but are also found on T cells [...]

Common symptoms of overt hypothyroidism are non-specific and include fatigue, lethargy, and dry skin. Although the diagnosis is considered to be straightforward, no single symptom can be used to identify patients with overt hypothyroidism, while many patients with subclinical hypothyroidism are asymptomatic. A large population-based study on the spectrum of symptoms in subclinical hypothyroidism showed similar rates of thyroid disease-related symptoms compared with euthyroid subjects, while the TSH concentration had no impact on symptom score. Together, these findings make it challenging to attribute symptoms to their underlying cause. This is also true in the case of unexplained persistent symptoms in levothyroxine-treated patients. Although generally considered a life-long replacement therapy, successful thyroid hormone discontinuation resulting in euthyroidism has been reported in approximately one third of patients. Thus, we overtreat patients with (subclinical) hypothyroidism, highlighting the importance of reliable diagnostic criteria. The diagnostic process, including the implementation of robust TSH and FT4 reference intervals, is especially challenging in specific situations including aging, pregnancy, non-thyroidal illness, and central hypothyroidism. There is a clear need for improved adherence to current guidelines from scientific societies and for willingness to manage symptoms without a clear pathological correlate, especially in the case of mild TSH elevations. This review will highlight recent literature on this topic and offers some practice points.

Neural stem cells in the murine subventricular zone (SVZ) reactivate during postnatal development to generate neurons and glia throughout adulthood. We previously demonstrated that a postnatal thyroid hormone (TH) peak orchestrates this remodelling, rendering this process vulnerable to endocrine disruption. We exposed mice to 2 or 200 µg/kg bw/day of the bisphenol A-replacement and suspected TH-disruptor bisphenol F (BPF) in the drinking water, from embryonic day 15 to postnatal day 21 (P21). In parallel, one group was exposed to the TH-synthesis blocker propylthiouracil (0.15 % PTU). In contrast to PTU, BPF exposure did not affect serum TH levels at P15, P21 or P60. RNA-seq on dissected SVZs at P15 revealed dysregulated neurodevelopmental genes in all treatments, although few overlapped amongst the conditions. We then investigated the phenotype at P60 to analyse long-term consequences of transient developmental exposure. As opposed to hypothyroid conditions, and despite dysregulated oligodendrogenesis-promoting genes in the P15 SVZ exposed to the highest dose of BPF, immunostainings for myelin and OLIG2/CC1 showed no impact on global myelin content nor oligodendrocyte maturation in the P60 corpus callosum, apart from a reduced thickness. The highest dose did reduce numbers of newly generated SVZ-neuroblasts with 22 %. Related to this were behavioural alterations. P60 mice previously exposed to the highest BPF dose memorized an odour less well than control animals did, although they performed better than PTU-exposed animals. All mice could discriminate new odours, but all exposed groups showed less interest in social odours. Our data indicate that perinatal exposure to low doses of BPF disrupts postnatal murine SVZ remodelling, and lowers the adult neuron/oligodendroglia output, even after exposure had been absent for 40 days. These anomalies warrant further investigation on the potential harm of alternative bisphenol compounds for human foetal brain development.

Commemorative events, organized in the aftermath of war or large-scale violence, can have an emotional impact on those who are attending. We examined several characteristics that might influence this impact. In a quasi-experimental pretest-posttest study, participants (n = 307) watched footage of the broadcast of the Dutch National Commemoration, in which World War II is remembered. A control group of 48 participants watched the commemoration broadcast live on Remembrance Day. They were matched for age, gender, war experience and migration background with 48 participants from the study group who watched the footage, to conduct a comparability check. We found some evidence that watching the footage was comparable to watching the commemoration live on Remembrance Day in terms of emotional response and experience of psychosocial factors. Participants in the footage sample (n = 307) responded with an increase of negative and decrease of positive emotions. Individual characteristics were limitedly related to the emotional response; posttraumatic stress symptom severity predicted increased negative emotions. Experiencing meaning making, support and, to a lesser extent, recognition through commemorating was related to experiencing more positive emotions. The findings indicate these psychosocial factors may buffer the emotional distress elicited by commemoration and contribute to important cognitive and social benefits. Practical implications are discussed.

Within health professional education around the world, there exists a growing awareness of the professional duty to be socially responsible, being attentive to the needs of all members of communities, regions, and nations, especially those who disproportionately suffer from the adverse influence of social determinants. However, much work still remains to progress beyond such good intentions. Moving from contemplation to action means embracing social accountability as a key guiding principle for change. Social accountability means that health institutions attend to improving the performance of individual practitioners and health systems by directing educational and practice interventions to promote the health of all the public and assessing the systemic effects of these interventions. In this Reflection, the authors (1) review the reasons why health professional schools and their governing bodies should codify, in both curricular and accreditation standards, norms of excellence in social accountability, (2) present four considerations crucial to successfully implementing this codification, and (3) discuss the challenges such changes might entail. The authors conclude by noting that in adopting socially accountable criteria, schools will need to expand their philosophical scope to recognize social accountability as a vitally important part of their institutional professional identity.

The functions of human NK cells in defense against pathogens and placental development during reproduction are modulated by interactions of killer cell Ig-like receptors (KIRs) with HLA-A, -B and -C class I ligands. Both receptors and ligands are highly polymorphic and exhibit extensive differences between human populations. Indigenous to southern Africa are the KhoeSan, the most ancient group of modern human populations, who have highest genomic diversity worldwide. We studied two KhoeSan populations, the Nama pastoralists and the ≠Khomani San hunter-gatherers. Comprehensive next-generation sequence analysis of HLA-A, -B, and -C and all KIR genes identified 248 different KIR and 137 HLA class I, which assort into ∼200 haplotypes for each gene family. All 74 Nama and 78 ≠Khomani San studied have different genotypes. Numerous novel KIR alleles were identified, including three arising by intergenic recombination. On average, KhoeSan individuals have seven to eight pairs of interacting KIR and HLA class I ligands, the highest diversity and divergence of polymorphic NK cell receptors and ligands observed to date. In this context of high genetic diversity, both the Nama and the ≠Khomani San have an unusually conserved, centromeric KIR haplotype that has arisen to high frequency and is different in the two KhoeSan populations. Distinguishing these haplotypes are independent mutations in KIR2DL1, which both prevent KIR2DL1 from functioning as an inhibitory receptor for C2+ HLA-C. The relatively high frequency of C2+ HLA-C in the Nama and the ≠Khomani San appears to have led to natural selection against strong inhibitory C2-specific KIR.

The functions of human NK cells in defense against pathogens and placental development during reproduction are modulated by interactions of killer cell Ig-like receptors (KIRs) with HLA-A, -B and -C class I ligands. Both receptors and ligands are highly polymorphic and exhibit extensive differences between human populations. Indigenous to southern Africa are the KhoeSan, the most ancient group of modern human populations, who have highest genomic diversity worldwide. We studied two KhoeSan populations, the Nama pastoralists and the ≠Khomani San hunter-gatherers. Comprehensive next-generation sequence analysis of HLA-A, -B, and -C and all KIR genes identified 248 different KIR and 137 HLA class I, which assort into ∼200 haplotypes for each gene family. All 74 Nama and 78 ≠Khomani San studied have different genotypes. Numerous novel KIR alleles were identified, including three arising by intergenic recombination. On average, KhoeSan individuals have seven to eight pairs of interacting KIR and HLA class I ligands, the highest diversity and divergence of polymorphic NK cell receptors and ligands observed to date. In this context of high genetic diversity, both the Nama and the ≠Khomani San have an unusually conserved, centromeric KIR haplotype that has arisen to high frequency and is different in the two KhoeSan populations. Distinguishing these haplotypes are independent mutations in KIR2DL1, which both prevent KIR2DL1 from functioning as an inhibitory receptor for C2+ HLA-C. The relatively high frequency of C2+ HLA-C in the Nama and the ≠Khomani San appears to have led to natural selection against strong inhibitory C2-specific KIR.

Abstract Background Inherent to anorexia nervosa are repetitive thoughts about weight and shape. Growing research suggests the relevance of intolerance of uncertainty and worry in maintaining these types of repetitive thoughts. The relation between these cognitive processes and weight and shape concerns in adolescent girls with anorexia nervosa is understudied. This study investigated associations between prospective (desire for predictability) and inhibitory (uncertainty paralysis) intolerance of uncertainty, and weight and shape concerns and the mediating role of worry in these associations. Methods In a cross-sectional study, 93 adolescent girls with anorexia nervosa completed questionnaires measuring the variables of interest. A mediation model with worry as a mediator between inhibitory and prospective intolerance of uncertainty and weight and shape concerns was tested. Results A total and direct effect of inhibitory intolerance of uncertainty on weight and shape concerns was found. Worry did not mediate this relation. Conclusions These results confirm the importance of inhibitory intolerance of uncertainty in adolescent girls with anorexia nervosa, more specifically to weight and shape concerns. This group may benefit from intervention strategies targeting intolerance of uncertainty. General worry seems less relevant to weight and shape concerns in adolescent girls with anorexia nervosa. Plain English summary Adolescent girls with anorexia nervosa often experience repetitive thoughts about weight and shape. Growing research suggests the relevance of intolerance of uncertainty and worry in maintaining these types of repetitive thoughts. Intolerance of uncertainty is defined as the incapacity to tolerate uncertainty and is often divided into two components; prospective intolerance of uncertainty (desire for predictability) and inhibitory intolerance of uncertainty (uncertainty paralysis). The relation between intolerance of uncertainty, worry and weight and shape concerns in adolescent girls with anorexia nervosa is understudied. This study aims to investigate study relations between prospective and inhibitory intolerance of uncertainty, worry, and weight and shape concerns. A total of 93 adolescent girls with anorexia nervosa completed three questionnaires, measuring prospective and inhibitory intolerance of uncertainty worry, and weight and shape concerns, respectively. The results of this study confirmed the importance of inhibitory intolerance of uncertainty in adolescent girls with anorexia nervosa, more specifically to weight and shape concerns. This group may benefit from intervention strategies targeting intolerance of uncertainty. General worry seems less relevant to weight and shape concerns in adolescent girls.

Abstract Background This study evaluated the feasibility of a short-term, multimodal trauma-focused treatment approach adapted specifically for unaccompanied refugee minors (URMs) in the Netherlands. This approach aims to overcome barriers to mental health care and to reduce symptoms of posttraumatic stress disorder (PTSD) and depression. Methods An uncontrolled study was conducted, evaluating the main request for help, treatment integrity and feasibility, and the course of symptoms of PTSD (Children's Revised Impact of Event Scale-13) and depression (Patient Health Questionnaire modified for Adolescents). Results In total, 41 minors were included in the study. Most participants were male (n = 27), predominately from Eritrea (75.6%) with a mean age of 16.5 (SD = 1.5). Minors mostly reported psychological problems, such as problems sleeping, and psychosocial problems, including worries about family reunification. Deviations from the approach were made to meet the current needs of the minors. Factors limiting the feasibility of the approach were often related to continuous stressors, such as news concerning asylum status. Conclusions The results provide a first indication that this approach partly overcomes barriers to mental health care and emphasize the added value of collaborating with intercultural mediators and offering outreach care. Trial registration: The study was registered in the Netherlands Trial Register (NL8585), 10 April 2020, Retrospectively registered, https://www.trialregister.nl/trial/8585 .

BackgroundPosttraumatic Stress Disorder (PTSD) is often reported by refugees that faced violence and persecution. Some stressful events may also entail moral conflicts or dilemmas, described as “potentially morally injurious events” (PMIE). Very few studies have yet investigated the nature of these PMIEs in traumatized refugees, using both quantitative and qualitative data.MethodFor this retrospective study, secondary data analysis was used to examine the traumatic events of 183 patients. Based on established definitions of a PMIE, participants were allocated to a Moral Injury (MI) group if they reported lasting distress after exposure to an event of which they indicated that it transgressed their moral beliefs. The remaining participants were allocated to the No-MI group. The type of PMIEs was categorized using qualitative analysis. The groups were compared in terms of PTSD severity, feelings of guilt, and general mental health symptoms.ResultsOf the total sample, 55 participants reported one or more acts of transgression (MI group) and 128 reported no acts of transgression (No-MI group). Analyses of PMIEs revealed six themes 1) failing to prevent harm to others, 2) not giving aid to people in need, 3) leaving family members behind that consequently lead to injury or death of others, 4) making indirect and direct moral decisions leading to injury or death of others, 5) betrayal, and 6) engaging in the harm of others. No differences were found between groups on the clinical outcomes, except for feelings of guilt.ConclusionA considerable number of traumatized refugees reported confrontation with PMIEs. Experiencing PMIEs appeared unrelated to elevated posttraumatic mental health issues.