The low mutational flexibility of the EPSP synthase in Bacillus subtilis is due to a higher demand for shikimate pathway intermediates.

Glyphosate (GS) inhibits the 5-enolpyruvyl-shikimate-3-phosphate (EPSP) synthase that is required for aromatic amino acid, folate and quinone biosynthesis in Bacillus subtilis and Escherichia coli. The inhibition of the EPSP synthase by GS depletes the cell of these metabolites, resulting in cell death. Here, we show that like the laboratory B. subtilis strains also environmental and undomesticated isolates adapt to GS by reducing herbicide uptake. Although B. subtilis possesses a GS-insensitive EPSP synthase, the enzyme is strongly inhibited by GS in the native environment. Moreover, the B. subtilis EPSP synthase mutant was only viable in rich medium containing menaquinone, indicating that the bacteria require a catalytically efficient EPSP synthase under nutrient-poor conditions. The dependency of B. subtilis on the EPSP synthase probably limits its evolvability. In contrast, E. coli rapidly acquires GS resistance by target modification. However, the evolution of a GS-resistant EPSP synthase under non-selective growth conditions indicates that GS resistance causes fitness costs. Therefore, in both model organisms, the proper function of the EPSP synthase is critical for the cellular viability. This study also revealed that the uptake systems for folate precursors, phenylalanine and tyrosine need to be identified and characterized in B. subtilis.

Over-Expression of LEDGF/p75 in HEp-2 Cells Enhances Autoimmune IgG Response in Patients with Benign Prostatic Hyperplasia-A Novel Diagnostic Approach with Therapeutic Consequence?

Lens epithelium-derived growth factor splice variant of 75 kDa (LEDGF/p75) is an autoantigen over-expressed in solid tumors and acts as a stress-related transcriptional co-activator. Participation of autoimmune responses in the pathophysiology of benign prostatic hyperplasia (PBH) and a corresponding immunosuppressive therapy by TNFalpha antagonists has been recently suggested. Thus, autoAb testing could aid in the diagnosis of BPH patients profiting from such therapy. We generated CRISPR/Cas9 modified HEp-2 LEDGF knock-out (KO) and HEp-2 LEDGF/p75 over-expressing (OE) cells and examined IgG autoantibody reactivity to LEDGF/p75 in patients with prostate cancer (PCa, n = 89), bladder cancer (BCa, n = 116), benign prostatic hyperplasia (BPH, n = 103), and blood donors (BD, n = 60) by indirect immunofluorescence assay (IFA). Surprisingly, we could not detect elevated binding of autoAbs against LEDGF/p75 in cancer patients, but autoAb reactivity to LEDGF/p75 OE cells in about 50% of patients with BPH was unexpectedly significantly increased. Furthermore, a line immunoassay enabling the detection of 18 different autoAbs revealed a significantly increased occurrence of anti-dsDNA autoAbs in 34% of BPH patients in contrast to tumor patients and BD. This finding was confirmed by anti-mitochondrial (mDNA) autoAb detection with the Crithidia luciliae immunofluorescence test, which also showed a significantly higher prevalence (34%) of anti-mDNA autoAbs in BPH. In summary, our study provided further evidence for the occurrence of autoimmune responses in BPH. Furthermore, LEDGF/p75 over-expression renders HEp-2 cells more autoantigenic and an ideal target for autoAb analysis in BPH with a potential therapy consequence.

Increased risk of somatic diseases following anorexia nervosa in a controlled nationwide cohort study.

OBJECTIVE: To assess the risk of somatic diseases in connection with anorexia nervosa (AN). METHOD: This matched cohort study was based on Danish registries of all patients born 1961-2008 with a first-time diagnosis of AN in 1994-2018 at age 8-32 and matched controls without an eating disorder. For 13 somatic disease categories, time from inclusion date to time of first somatic diagnosis, accounting for censoring, was studied by use of time-stratified Cox models. RESULTS: A total of 9985 AN patients born 1961-2008 and 49,351 controls were followed for a median (interquartile range) of 9.0 (4.4-15.7) years. During the first 2 years after entry there was a 60% higher hazard for any somatic disease among patients with AN than among controls, while the ratio from three to 11 years was reduced to 1.18. Regardless of age at diagnosis, the hazard among patients and controls were no different at approximately a decade after diagnosis of AN and the cumulative risk for patients for 12 of 13 disease categories was always higher or no less that for controls. For all disease categories, the hazard ratio (HR) was higher when close to entry. For most disease categories, age at diagnosis of AN did not modify the effect. DISCUSSION: While around 90% of all individuals had any somatic disease at the end of follow-up, the cumulative incidence over time was higher for patients with AN than for controls. Large HRs were seen in the early years after diagnosis during which patients require extensive medical interventions. PUBLIC SIGNIFICANCE: Based on Danish registries, a large sample of almost 10,000 patients with AN born 1961-2008 and almost 50,000 matched controls were followed for a median of 9 years. While around 90% of all individuals had any somatic disease at the end of follow-up, the cumulative incidence over time was higher for patients with AN than for controls.

Validating the Danish version of the Eating Disorder Quality of Life Scale (EDQLS) in anorexia nervosa.

PURPOSE: The aim of this study was to explore the factor structure of the Danish translation of the eating disorder quality of life scale and evaluate the internal reliability and convergent validity of the scale in a Danish cohort of women with AN. METHODS: The total sample comprised 211 patients diagnosed with anorexia nervosa age 13-40 years. Patients completed questionnaires assessing eating disorder psychopathology, physical and social functioning, and well-being. RESULTS: Factor analyses were not able to support the current division of the scale into 12 factors. We found excellent internal consistency of the eating disorder quality-of-life scale total score. We found relevant associations between quality of life and pre-determined variables. CONCLUSION: This study supports the use of the total score of the eating disorder quality of life scale in assessing quality of life in patients with anorexia nervosa. However, future studies should explore the factor structure of the scale further. LEVEL OF EVIDENCE: III: Evidence obtained from cohort or case-control analytic studies.

Comorbid mental disorders during long-term course in a nationwide cohort of patients with anorexia nervosa.

OBJECTIVE: Comorbid mental disorders in anorexia nervosa during long-term course require detailed studies. METHOD: This matched cohort study was based on nationwide Danish register data of all patients born 1961-2008 with a first-time ICD-10 diagnosis of anorexia nervosa (AN) between 1994 and 2018 at age 8-32 and matched controls taken from all individuals without an eating disorder (ED). For nine categories of non-eating mental disorders, time from date of first AN-diagnosis (inclusion date) to time of first diagnosis, accounting for censoring, was studied by use of time-stratified Cox models. RESULTS: A total of 9,985 patients with AN (93.5% females) and 49,351 matched controls were followed for a median (IQR) of 9.0 (4.4-15.7) years. For patients, there was about 25% and 55% risk of receiving any non-ED disorder during the first 2 years and two decades after inclusion, respectively. A hazard ratio (HR) of seven for any non-ED was found for the first 12 months after inclusion, a ratio that reduced to two at five or more years after inclusion. During the first years, large HRs ranging in 6-9 were found for affective, autism spectrum, personality, and obsessive-compulsive disorders with the latter displaying the highest continuous increased risk. The HR at 12 months after inclusion was highest for any non-ED disorder and affective disorders in patients aged 8-13 at diagnosis. DISCUSSION: Comorbid mental disorders in AN are most frequently diagnosed in the first years after diagnosis of AN and on longer terms imply a double immediate risk.

Assessment of fracture risk in women with eating disorders: The utility of dual-energy x-ray absorptiometry (DXA)-Clinical cohort study.

OBJECTIVE: Eating disorders (EDs) are associated with decreased bone mineral density (BMD) and increased fracture risk. The association between BMD and fracture risk in EDs is not well elucidated. We aimed to assess BMD in an ED cohort of patients with active disease and patients in remission, and to assess the predictive value of BMD on incidence of fractures. METHOD: We included 344 female patients (median age 19, IQR 16; 24) referred to ED treatment. Later, patients were invited to follow-up including assessment of remission status and a dual-energy x-ray absorptiometry (DXA)-scan. Information on fractures was obtained through the Danish National Registry of Patients. RESULTS: Patients with current anorexia nervosa (AN) had significantly lower BMD compared to controls at lumbar spine (16% lower, p < .0001), femoral neck (18% lower, p < .0001), and total hip (23% lower, p < .0001). Recovered AN patients had higher BMD compared to those with current disease (p < .0001 for all measures), but lower BMD compared to controls at lumbar spine (p < .01) and hip (p < .001). BMD did not differ between BN patients and controls. In patients with active eating disorders not otherwise specified, BMD was lower only at the total hip (p < .005). We found no association between BMD and fracture risk. CONCLUSION: We confirm that AN is associated with low BMD, whereas BN is not. Remission is associated with higher BMD compared to patients with active AN, but a deficit remains. We found no significant association between BMD and fracture risk, challenging the benefit of the widespread use of DXA scans in young women with ED. CLINICAL TRIAL REGISTRATION: The study is registered in ClinicalTrials.gov, number NCT00267228.

Fractures in women with eating disorders-Incidence, predictive factors, and the impact of disease remission: Cohort study with background population controls.

OBJECTIVE: Malnutrition and low weight in eating disorders (EDs) are associated with increased fracture risk compared to the general population. In a cohort study, we aimed to determine fracture rates compared to age and gender matched controls (ratio 5:1), assess the impact of disease remission on fracture risk, and establish predictive factors for fractures. METHOD: Of note, 803 ED patients referred to specialized ED treatment between 1994 and 2004 were included. In 2016, data on fractures were obtained through the Danish National Registry of Patients. RESULTS: Fracture risk was increased in anorexia nervosa (AN; IRR 2.2 [CI 99%: 1.6-3.0]) but not in bulimia nervosa (BN; IRR 1.3, ns) or other specified feeding or eating disorders (OSFED; IRR 1.8, ns). IRR in the AN group were increased for vertebral fractures (IRR 3.8 [CI 99%: 1.4-10.3]), upper arm (IRR 3.0 (CI 99% 1.6-5.5) and hip (IRR 6.6 [CI 99%: 2.6-18.0]). Disease remission in AN is associated to lower fracture risk compared to active disease, but higher fracture risk compared to controls (IRR 1.7 [CI 99%: 1.1-2.7]). In regression analysis, age at debut of disease, nadir BMI and duration of disease before referral to treatment, independently predicted fracture. DISCUSSION: We confirm increased fracture risk in AN, and show significant differences in fracture risk between patients in disease remission and patients with active disease. Furthermore, we show that age at debut of disease and duration of disease before referral to treatment is positively correlated to fracture risk, whereas nadir BMI is negatively correlated to fracture risk.

Time trends in treatment modes of anorexia nervosa in a nationwide cohort with free and equal access to treatment.

BACKGROUND: Treating patients with anorexia nervosa (AN) remains a major challenge. The choice between an inpatient or an outpatient care setting is an essential issue for the patients and for their relatives with major health economic implications. However, health services-related studies are lacking. The present study was a descriptive exploration of time-trends in treatment modes of patients with free and equal access to health services. METHODS: The study was based on a nationwide cohort of patients diagnosed for the first time with AN, each followed for 5 years in the registers covering the years 1994-2018. The per patient number of hospital admissions, cumulated number of days of hospitalization and number of outpatient visits during the first 5 years after initial diagnosis were considered. RESULTS: The cohort of patients with AN with at least 5 years of follow-up amounted to N = 7,505. A clear trend was observed in the per patient five-year cumulated number of inpatient days, decreasing by 6% per year after adjustment for age at diagnosis, parental mental diagnosis, and family income. The five-year number of hospital admissions after initial diagnosis decreased by 2% per year, while no trend was observed for outpatient visits. CONCLUSIONS: The per patient number of hospitalizations and cumulated days of hospitalization during 5 years after diagnosis were reduced for patients initially diagnosed with AN while there was no change in the number of outpatient visits. The factors contributing to these changes of treatment modes over time are in need of further study.

Hunger and satiety perception in patients with severe anorexia nervosa.

OBJECTIVES: Appetite is a subjective essential sense. In patients with severe anorexia nervosa (AN), controversy remains whether this sensation is altered. The objectives were to clarify, in patients with severe AN: (1) Whether the appetite changes during partial weight restoration, (2) Whether potential changes in appetite are related to (i) diagnostic subtype of AN, (ii) psychopharmacological treatment, (iii) disease duration, (iv) duration of hospitalization, and (v) baseline body mass index (BMI). METHODS: The study consisted of 39 patients, with a mean age of 23.7 ± 8 and an admission mean BMI of 13.1 ± 2.0 kg/m2. The patients were consecutively admitted to a specialized somatic nutrition unit between 2015 and 2016. They were asked to rate their hunger and satiety on a numeric visual analog scale (VAS), before and after a lunch meal at admission and at discharge in the same standardized environment. The patients could participate more than once if readmitted, resulting in a total of 119 observed meals. Data were analyzed in a regression model for repeated measures. RESULTS: At admission, changes in hunger and satiety perception were weak. After weight gain of 10.4% ± 8.5% within a median of 26 (IQR: 25) days, there was a slight increase in hunger perception, p = 0.049. However, there was no detectable change in satiety perception. There was no noticeable correlation between appetite change and psychopharmacological treatment, diagnostic subtype, BMI, duration of hospitalization, and disease duration. CONCLUSION: Hospitalized patients with severe AN exhibit strikingly weak changes in hunger and satiety perception during standardized and supervised meals. LEVEL OF EVIDENCE: Level IV, evidence obtained from multiple time series analysis.

The Role of Body Weight on Bone in Anorexia Nervosa: A HR-pQCT Study.

Anorexia nervosa (AN) is associated with decreased bone mineral density and increased risk of fracture. The aim of this study was to assess bone geometry, volumetric bone mineral density (vBMD), trabecular microarchitecture and estimated failure load in weight-bearing vs. non-weight-bearing bones in AN. We included twenty-five females with AN, and twenty-five female controls matched on age and height. Bone geometry, vBMD and trabecular microarchitecture were assessed using high-resolution peripheral quantitative computed tomography of the distal radius and tibia. At both sites, cortical perimeter and total bone area were similar in patients and controls. Total vBMD was lower in the AN group in the tibia (p < 0.0005) but not in the radius. In the tibia, cortical thickness was approximately 25% lower (p < 0.0005) in the AN group, whereas there was no significant difference in the radius. In terms of trabecular microarchitecture, all indices [bone volume/tissue volume (BV/TV); trabecular thickness (Tb.Th.), trabecular number (Tb.N) and trabecular spacing (Tb.Sp.)] were impaired in AN in the tibia (p values range < 0.01-0.0001). In the radius, BV/TV and Tb.N were lower (p < 0.05 and p < 0.001, respectively); Tb.Sp. was higher (p < 0.001), whereas Tb.Th. did not differ, compared to controls. Estimated failure load was lower in patients in both the radius and the tibia (p < 0.0005 and p < 0.0001, respectively), most pronounced in the tibia. In conclusion, the impairment of cortical thickness and estimated failure load were significantly more pronounced in the weight-bearing tibia, compared to the non-weight-bearing radius, implying a direct effect of low body weight on bone loss in AN.

Body composition and menstrual status in adults with a history of anorexia nervosa-at what fat percentage is the menstrual cycle restored?

OBJECTIVE: To study the association between body composition measures and menstrual status in a large sample of adult patients with a history of anorexia nervosa and to calculate the predicted probability of resumption of menstrual function. Furthermore, to establish whether fat percentage is superior to body mass index in predicting the resumption of menses. METHOD: One hundred and thirteen adult women with a history of anorexia nervosa underwent a dual energy X-ray absorptiometry (DXA) scan and completed questionnaires regarding medication prescription and menstrual function. RESULTS: Fifty percent of patients were expected to resume their menstrual function at a body mass index of 19 kg m-2 or a fat percentage of 23%. Twenty-five percent of patients were expected to resume their menstrual function at body mass index 14 kg m-2 or fat percentage 11%. Fat percentage and body mass index were equally capable of predicting the resumption of menses. DISCUSSION: Fat percentage and body mass index were positive predictors of the resumption of menses, however, body composition measured by dual energy X-ray absorptiometry was not superior to body mass index in predicting menstrual recovery, which is of great clinical relevance as body mass index is easier and cheaper to obtain. Body composition measures only account for one of numerous factors involved in the resumption of menses. Regression models based on our data had a R2 value of 0.14, indicating that only 14% of the variation in menstrual recovery could be explained by the variables included. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2017; 50:370-377).

The 19S proteasome activator promotes human cytomegalovirus immediate early gene expression through proteolytic and nonproteolytic mechanisms.

Proteasomes are large, multisubunit complexes that support normal cellular activities by executing the bulk of protein turnover. During infection, many viruses have been shown to promote viral replication by using proteasomes to degrade cellular factors that restrict viral replication. For example, the human cytomegalovirus (HCMV) pp71 protein induces the proteasomal degradation of Daxx, a cellular transcriptional repressor that can silence viral immediate early (IE) gene expression. We previously showed that this degradation requires both the proteasome catalytic 20S core particle (CP) and the 19S regulatory particle (RP). The 19S RP associates with the 20S CP to facilitate protein degradation but also plays a 20S CP-independent role promoting transcription. Here, we present a nonproteolytic role of the 19S RP in HCMV IE gene expression. We demonstrate that 19S RP subunits are recruited to the major immediate early promoter (MIEP) that directs IE transcription. Depletion of 19S RP subunits generated a defect in RNA polymerase II elongation through the MIE locus during HCMV infection. Our results reveal that HCMV commandeers proteasome components for both proteolytic and nonproteolytic roles to promote HCMV lytic infection. Importance: Proteasome inhibitors decrease or eliminate 20S CP activity and are garnering increasing interest as chemotherapeutics. However, an increasing body of evidence implicates 19S RP subunits in important proteolytic-independent roles during transcription. Thus, pharmacological inhibition of the 20S CP as a means to modulate proteasome function toward therapeutic effect is an incomplete capitalization on the potential of this approach. Here, we provide an additional example of nonproteolytic 19S RP function in promoting HCMV transcription. These data provide a novel system with which to study the roles of different proteasome components during transcription, a rationale for previously described shifts in 19S RP subunit localization during HCMV infection, and a potential therapeutic intervention point at a pre-immediate early stage for the inhibition of HCMV infection.

Ubiquitin-independent proteasomal degradation of tumor suppressors by human cytomegalovirus pp71 requires the 19S regulatory particle.

Proteasomes generally degrade substrates tagged with polyubiquitin chains. In rare cases, however, proteasomes can degrade proteins without prior ubiquitination. For example, the human cytomegalovirus (HCMV) pp71 protein induces the proteasome-dependent, ubiquitin-independent degradation of the retinoblastoma (Rb) and Daxx proteins. These transcriptional corepressors and tumor suppressors inhibit the expression of cellular or viral genes that are required for efficient viral replication. Proteasomes are composed of a 20S catalytic core with or without one or two activator complexes, of which there are four different types. Here, we show that only one of these activators, the 19S regulatory particle that normally participates in ubiquitin-dependent protein degradation, is required for pp71-mediated degradation of Rb and Daxx. We report the unique use of a well-established route of substrate delivery to the proteasome by a viral protein to promote infection.

MicroRNA regulation of the serine synthesis pathway in endocrine-resistant breast cancer cells.

Despite the successful combination of therapies improving survival of estrogen receptor α (ER+) breast cancer patients with metastatic disease, mechanisms for acquired endocrine resistance remain to be fully elucidated. The RNA binding protein HNRNPA2B1 (A2B1), a reader of N(6)-methyladenosine (m6A) in transcribed RNA, is upregulated in endocrine-resistant, ER+ LCC9 and LY2 cells compared to parental MCF-7 endocrine-sensitive luminal A breast cancer cells. The miRNA-seq transcriptome of MCF-7 cells overexpressing A2B1 identified the serine metabolic processes pathway. Increased expression of two key enzymes in the serine synthesis pathway (SSP), phosphoserine aminotransferase 1 (PSAT1) and phosphoglycerate dehydrogenase (PHGDH), correlates with poor outcomes in ER+ breast patients who received tamoxifen (TAM). We reported that PSAT1 and PHGDH were higher in LCC9 and LY2 cells compared to MCF-7 cells and their knockdown enhanced TAM sensitivity in these-resistant cells. Here we demonstrate that stable, modest overexpression of A2B1 in MCF-7 cells increased PSAT1 and PHGDH and endocrine resistance. We identified four miRNAs downregulated in MCF-7-A2B1 cells that directly target the PSAT1 3'UTR (miR-145-5p and miR-424-5p), and the PHGDH 3'UTR (miR-34b-5p and miR-876-5p) in dual luciferase assays. Lower expression of miR-145-5p and miR-424-5p in LCC9 and ZR-75-1-4-OHT cells correlated with increased PSAT1 and lower expression of miR-34b-5p and miR-876-5p in LCC9 and ZR-75-1-4-OHT cells correlated with increased PHGDH. Transient transfection of these miRNAs restored endocrine-therapy sensitivity in LCC9 and ZR-75-1-4-OHT cells. Overall, our data suggest a role for decreased A2B1-regulated miRNAs in endocrine resistance and upregulation of the SSP to promote tumor progression in ER+ breast cancer.

Ubiquitin-independent proteasomal degradation during oncogenic viral infections.

Most eukaryotic proteins destined for imminent destruction are first tagged with a chain of ubiquitin molecules and are subsequently dismantled by the proteasome. Ubiquitin-independent degradation of substrates by the proteasome, however, also occurs. The number of documented proteasome-dependent, ubiquitin-independent degradation events remains relatively small but continues to grow. Proteins involved in oncogenesis and tumor suppression make up the majority of the known cases for this type of protein destruction. Provocatively, viruses with confirmed or suspected oncogenic properties are also prominent participants in the pantheon of ubiquitin-independent proteasomal degradation events. In this review, we identify and describe examples of proteasome-dependent, ubiquitin-independent protein degradation that occur during tumor virus infections, speculate why this type of protein destruction may be preferred during oncogenesis, and argue that this uncommon type of protein turnover represents a prime target for antiviral and anticancer therapeutics.

Explanatory Factors for Disease-Specific Health-Related Quality of Life in Women with Anorexia Nervosa.

A better understanding of explanatory factors for disease-specific health-related quality of life (HRQoL) in anorexia nervosa (AN) could help direct treatment providers to aspects of the most relevance for patient wellbeing and recovery. We aimed to investigate whether factors associated with HRQoL are the same for women with AN and normal-weight controls. The participants in this study were women with AN recruited from specialized eating disorder centers in Denmark and healthy, normal-weight controls invited via online social media. Participants completed online questionnaires on medical history, disease-specific HRQoL (Eating Disorders Quality of Life Scale, EDQLS) and generic HRQoL (SF-36), eating disorder symptomatology, depression, psychological wellbeing, and work and social adjustment. Questionnaires were fully completed by 211 women with AN (median age 21.7 years) and 199 controls (median age 23.9 years). Women with AN had poorer scores on all measures, i.e., worse HRQoL, psychological health, and work/social functioning. Eating disorder symptomatology affected EDQLS score in both groups, but poorer HRQoL in women with AN was also significantly associated with worse scores on bulimia, maturity fears, depression, vitality, and with older age. The factors investigated together explained 79% of the variance in EDQLS score. Management of disordered self-assessment and thought processes may be of particular importance to women with AN. Greater emphasis on these aspects alongside weight gain could enhance patient-clinician alliance and contribute to better treatment outcomes.

Slow-growing craniopharyngioma masquarading as early-onset eating disorder: two cases.

BACKGROUND: Craniopharyngiomas are slow-growing tumors, which can either be asymptomatic or present themselves with visual, neuropsychiatric or endocrine disturbances. Eating disorders (EDs) are syndromes with unknown etiology, associated with multiple endocrine abnormalities. In pediatric cases the presentation of EDs may differ markedly from those of adults. OBJECTIVE: We report on two pediatric patients with craniopharyngioma misinterpreted as ED. METHOD: Available patient records, psychiatric examinations, neuro-radiographic imaging, and biochemical data were evaluated. DISCUSSION: The reported cases illustrate the importance to consider slow-growing craniopharyngioma in ED. Especially in atypical ED, neuro-radiographic, ophthalmologic and endocrine examination should be carried out. Furthermore, structural hypothalamic lesions in these cases mimicking features of ED, suggesting the possibility of an as yet unidentified structural hypothalamic disorder to be implicated in the etiopathogeny of ED.

A Danish translation of the eating disorder quality of life scale (EDQLS).

BACKGROUND: In Denmark, only generic health-related quality of life measures have been developed to assess quality of life in patients with eating disorders. So far, no disease-specific questionnaires have been translated and validated. The objective of this study was to translate the Eating Disorders Quality of Life Scale into Danish and to perform a preliminary validation of the questionnaire in a small sample. METHODS: The translation process was conducted according to recommendations from the World Health Organization, using the WHO-5 Well-Being Index as a reference standard. The validation process included 41 outpatients with eating disorders. Patients were recruited from specialized outpatient clinics in the Capital Region of Denmark and asked to complete the quality of life questionnaire and the WHO-5 Well-Being Index. RESULTS: This study found poor agreement, but high correlation, between the two self-rating scales. CONCLUSION: The translated questionnaire was concluded to be valid. However, a replication study on a larger sample with more male patients and more extensive symptoms is necessary.

Funen Anorexia Nervosa Study - a follow-up study on outcome, mortality, quality of life and body composition.

Eating disorders (EDs) comprise a wide range of symptoms, with severe psychological and physical implications for the patient. EDs include anorexia nervosa (AN), bulimia nervosa (BN) and until 2013 eating disorder not otherwise specified (EDNOS), if criteria for AN or BN were not met. Patients suffering from an ED have poor prognosis, with more than half of AN patients not obtaining complete remission. One-fifth develops a chronic disease. EDs have an increased risk of premature death and patients with EDs report poorer quality of life (QoL) compared to both the general population and other psychiatric/somatic diseases. Patients who, apparently, obtain complete remission will still be affected in QoL when compared to a healthy reference group. Treatment is complicated by high drop-out rates, hence making large retrospective follow-up studies difficult to conduct. The multiple endocrine disturbances as a result of the severe malnourishment in AN often result in amenorrhea and a weight goal for remenorrhea has been ambiguous. This thesis encompasses results from four studies examining the abovementioned challenges and is based on a large retrospective cohort of ED patients referred to a highly specialized ED treatment unit. Study 1: QoL in EDs was reported for a large retrospective Danish cohort. Furthermore, meta-analysis on existing published literature was performed to determine potential differences between the diagnostic groups. QoL in EDs was significantly decreased compared to the general population and no difference between the diagnostic groups was established. Study 2: ED pathology (measured by the Eating Disorder Inventory - 2 (EDI-2)) and outcome (measured by the Morgan Russell Outcome Schedule (MROS)) was reported for a large retrospective Danish cohort. The correlation between the patient-reported measurements (SF-36 & EDI-2) and clinician-assessed characteristics (BMI and remission status) was investigated in a group of ED patients (n=383). A high association between EDI scores and BMI was observed in AN and EDNOS, despite remission status, representing an increase in symptomatology with increasing BMI. This was not present in BN. We found no association between HRQoL and BMI in any of the diagnostic groups. Study 3:  Mortality rates were calculated in a large group of ED patients (n=998) including AN, BN and EDNOS with a long follow-up time. We found a SMR of 2.9 for AN, which was considerably lower than previous published results. We compared the results to data from the same catchment area published prior to the establishment of a multidisciplinary ED center. Patients with EDs had a significantly increased risk of premature death compared to the general population; however the mortality rates had decreased since the formation of the ED unit. Study 4: The association between body composition measures and amenorrhea was studied in a cohort of adult patients with a history of AN (n=113) and predicted probabilities for the resumption of menses was determined. We found a high association between DXA scans and BMI in predicting the resumption of menses. Half of the patients were predicted to resume their menstrual status at BMI 19/fat percentage 23, however at BMI 14/fat percentage 11 still 25% of patients were predicted to resume their menses.

Patient- and clinician- reported outcome in eating disorders.

Patient-reported outcome is increasingly applied in health sciences. Patients with eating disorders (EDs) characteristically have a different opinion of their needs to that of the health professionals, which can lead to ambivalence towards treatment and immense compliance difficulties. This cross-sectional study compared data assessed by the clinician to patient-reported measures in patients with a history of EDs. We included data from a cohort of patients with EDs (n=544) referred to a specialized ED unit in Denmark. Patient-reported measures included the Eating Disorder Inventory-2 (EDI-2) and the Short Form 36 (SF-36), and clinical data included remission status and body mass index (BMI). We found a positive association between BMI and EDI-2 scores for anorexia nervosa (AN) and eating disorder not otherwise specified (EDNOS), reflecting increasing ED symptomatology with increasing BMI. This association was not observed in bulimia nervosa (BN). We did not find a correlation between SF-36 scores and BMI in any of the diagnostic groups.