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Oxidative DNA damage is recognized by 8-oxoguanine (8-oxoG) DNA glycosylase 1 (OGG1), which excises 8-oxoG, leaving a substrate for apurinic endonuclease 1 (APE1) and initiating repair. Here, we describe a small molecule (TH10785) that interacts with the phenylalanine-319 and glycine-42 amino acids of OGG1, increases the enzyme activity 10-fold, and generates a previously undescribed β,δ-lyase enzymatic function. TH10785 controls the catalytic activity mediated by a nitrogen base within its molecular structure. In cells, TH10785 increases OGG1 recruitment to and repair of oxidative DNA damage. This alters the repair process, which no longer requires APE1 but instead is dependent on polynucleotide kinase phosphatase (PNKP1) activity. The increased repair of oxidative DNA lesions with a small molecule may have therapeutic applications in various diseases and aging.

The objective of this paper is to evaluate the accuracy of the NASA BioSentinel Pixel Dosimeter (BPD) using gamma-ray and neutron sources in a standard calibration lab. The dosimeter tested here is the ground-based version of the BPD that will be onboard the BioSentinel mission. The BPD was exposed to radiation from (60)Co, (137)Cs, and (252)Cf at selected distances (dose rates) at the Lawrence Livermore National Laboratory (LLNL) Radiation Calibration Laboratory (RCL), and the results were compared with NIST traceable benchmark values. It is recognized that these sources are not analogs for the space environment but do provide direct comparisons between BPD response and well characterized calibration lab values. For gamma rays, the BPD measured absorbed dose agrees to ≤ 3.8% compared with RCL benchmark values. For neutrons, the results show that the BPD is insensitive, i.e., the BPD detected only the gamma-ray dose component from (252)Cf. The LET spectra obtained for gamma rays from (60)Co and (252)Cf are consistent with expectations for these gamma-ray energies, but the LET spectrum from the (137)Cs gamma rays differs substantially. The potential causes for this difference are the high dose rate from (137)Cs and the lower secondary electron energy produced by (137)Cs gamma rays. However, neither of these results in errors in the absorbed dose. Based on comparisons with NIST-traceable standards, it is evident that the BPD can measure absorbed dose accurately from low LET charged particles. The sensor’s insensitivity to neutrons is unlikely to be a limitation for the BioSentinel mission due to the expected low secondary neutron fluence.

Purpose Suboptimal vitamin D levels are implicated in low bone mineral density, a common medical complication of anorexia nervosa. This study aimed to examine the frequency of vitamin D assessment and treatment for adolescents with anorexia nervosa in outpatient medical management. Design and methods Retrospective chart review was used to examine 179 adolescents (M age = 15.5 years, SD = 2.2), newly diagnosed with anorexia nervosa at a tertiary care medical center in the United States between January 2000 and July 2016. Results Only 16% of patients (n = 29) received serum vitamin D assessments following diagnosis, of whom 52% had suboptimal vitamin D levels (n = 15). Only three patients with suboptimal vitamin D were advised to begin supplementation. No patients in our sample were encouraged to begin prophylactic vitamin D supplementation. Conclusions/practice implications Findings from this study highlight the critical need for widespread care team education about vitamin D assessment and treatment in the medical management of adolescents with anorexia nervosa, particularly in light of the potentially serious consequences of bone mineral density.

Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is a mitochondrial 1-carbon metabolism enzyme, which is an attractive anticancer drug target as it is highly upregulated in cancer but is not expressed in healthy adult cells. Selective MTHFD2 inhibitors could therefore offer reduced side-effects during treatment, which are common with antifolate drugs that target other 1C-metabolism enzymes. This task is challenging however, as MTHFD2 shares high sequence identity with the constitutively expressed isozymes cytosolic MTHFD1 and mitochondrial MTHFD2L. In fact, one of the most potent MTHFD2 inhibitors reported to date, TH7299, is actually more active against MTHFD1 and MTHFD2L. While structures of MTHFD2 and MTHFD1 exist, no MTHFD2L structures are available. We determined the first structure of MTHFD2L and its complex with TH7299, which reveals the structural basis for its highly potent MTHFD2L inhibition. Detailed analysis of the MTHFD2L structure presented here clearly highlights the challenges associated with developing truly isoform-selective MTHFD2 inhibitors.

Adverse childhood experiences are associated with impaired physical health in adulthood. Using data from the Midlife in the United States survey (N = 4041), this study examined whether four dimensions of religiosity moderated the long-term detrimental effects of early adversity on three distinct aspects of adult physical health (self-rated health, functional limitations, and shortness of breath). Regression analyses showed that religious support buffered the effect of childhood adversity on physical health, but religious identification, private religious practice, or religious service attendance did not. Results imply that interventions aimed at increasing religious support can be effective decades after the adverse experiences took place.

The use of tyrosine kinase inhibitors (TKIs) targeting the BCR-ABL fusion protein have dramatically changed the clinical management and outcomes for patients with chronic myelogenous leukemia (CML)...

Culture is believed to play a central role in body image and eating problems, and for this reason, it is important to conduct cross-cultural investigations of relevant theoretical models. This study involves a non-Western replication of one of the few existing models of positive body image, the gratitude model of body appreciation, which was originally developed using American women. The model postulates that a grateful attitude is associated with body appreciation and intuitive eating via reduced contingent self-worth and social comparison. The current study aims to examine the applicability of the model to Japanese women. A sample of 648 Japanese women (age range = 15–69, M = 42.1, SD = 15.7) completed online measures of gratitude, contingent self-worth, social comparison, body appreciation, and intuitive eating. In general, all paths in the original model were replicated in the current model. However, two new paths were added to achieve good fit, including a path from basing one’s self-worth on others’ approval to body appreciation and another path from gratitude directly to intuitive eating. These differential pathways are discussed in the context of Japanese culture that emphasizes appreciation towards foods and self-definition based on social approval. In addition, implications for intervention are described.

The high global burden of cryptococcosis has made development of a protective vaccine a public health priority. We previously demonstrated that a vaccine composed of recombinantCryptococcus neoformanschitin deacetylase 2 (Cda2) delivered in glucan particles (GPs) protects BALB/c and C57BL/6 mice from an otherwise lethal challenge with a highly virulentC. neoformansstrain. An immunoinformatic analysis of Cda2 revealed a peptide sequence predicted to have strong binding to the MHC Class II (MHC II) H2-IAd allele found in BALB/c mice. BALB/c mice vaccinated with GPs containing a 32 amino acid peptide (Cda2-Pep1) that included this strong binding region were protected from cryptococcosis. Protection was lost with GP-based vaccines containing versions of recombinant Cda2 protein and Cda2-Pep1 with mutations predicted to greatly diminish MHC II binding. Cda2 has homology to the three otherC. neoformanschitin deacetylases, Cda1, Cda3 and Fpd1, in the high MHC II binding region. GPs loaded with homologous peptides of Cda1, Cda3 and Fpd1 protected BALB/c mice from experimental cryptococcosis, albeit not as robustly as the Cda2-Pep1 vaccine. Finally, seven other peptides were synthesized based on regions in Cda2 predicted to contain promising CD4+T cell epitopes in BALB/c or C57BL/6 mice. While five peptide vaccines significantly protected BALB/c mice, only one protected C57BL/6 mice. Thus, GP-based vaccines containing a single peptide can protect mice against cryptococcosis. However, given the diversity of human MHC II alleles, a peptide-basedCryptococcusvaccine for use in humans would be challenging and likely need to contain multiple peptide sequences.ImportanceCryptococcosis, due to infection by fungi of theCryptococcus neoformansspecies complex, is responsible for substantial morbidity and mortality in immunocompromised persons, particularly those with AIDS. Cryptococcal vaccines are a public health priority yet are not available for human use. We previously demonstrated mice could be protected from experimental cryptococcosis with vaccines composed of recombinant cryptococcal proteins encased in hollow highly purified yeast cell walls (glucan particles). Here, we examined one such protective protein, Cda2, and using bioinformatics, identified a region predicted to stimulate strong T cell responses. A peptide containing this region formulated in glucan particle-based vaccines protected mice as well as the recombinant protein. Other peptide vaccines also protected, including peptides containing sequences from proteins homologous to Cda2. These preclinical mouse studies provide a proof of principle that peptides can be effective as vaccines to protect against cryptococcosis and that bioinformatic approaches can guide peptide selection.

We present a spectral analysis of NuSTAR and NICER observations of the luminous, persistently accreting neutron star (NS) low-mass X-ray binary Cygnus X-2. The data were divided into different branches that the source traces out on the Z-track of the X-ray color-color diagram; namely the horizontal branch, normal branch, and the vertex between the two. The X-ray continuum spectrum was modeled in two different ways that produced a comparable quality fit. The spectra showed clear evidence of a reflection component in the form of a broadened Fe K line, as well as a lower energy emission feature near 1 keV likely due to an ionized plasma located far from the innermost accretion disk. We account for the reflection spectrum with two independent models (relxillns and rdblur*rfxconv). The inferred inclination is in agreement with earlier estimates from optical observations of ellipsoidal light curve modeling (relxillns: $i=67^{\circ}\pm4^{\circ}$, rdblur*rfxconv: $i=60^{\circ}\pm10^{\circ}$). The inner disk radius remains close to the NS ($R_{\rm in}\leq1.15\ R_{\mathrm{ISCO}}$) regardless of the source position along the Z-track or how the 1 keV feature is modeled. Given the optically determined NS mass of $1.71\pm0.21\ M_{\odot}$, this corresponds to a conservative upper limit of $R_{\rm in}\leq19.5$ km for $M=1.92\ M_{\odot}$ or $R_{\rm in}\leq15.3$ km for $M=1.5\ M_{\odot}$. We compare these radius constraints to those obtained from NS gravitational wave merger events and recent NICER pulsar light curve modeling measurements., Comment: Accepted for publication in ApJ, 13 pages, 5 tables, 5 figures

OBJECTIVES Evidence for the effectiveness of intensive interdisciplinary pain treatment (IIPT) for pediatric chronic pain is growing; however, little research has considered factors that contribute to differences in patients' treatment response. The present study utilized multilevel modeling to examine trajectory of change over time in functional disability from clinic assessment to 6-month follow-up in pediatric patients participating in IIPT, considering spatial distribution of pain, coping efficacy, and pain intensity. MATERIALS AND METHODS Participants included 110 pediatric patients (Mage=14.65, SD=2.37; localized pain, 27.3%; widespread pain, 72.7%) consecutively admitted into IIPT. Patients completed self-report measures of functional disability, pain intensity, and coping efficacy at pretreatment assessment, admission, weekly during IIPT, discharge, and several follow-ups. RESULTS Analysis identified a model with 3 three-way interactions, including time, time squared, pain intensity, coping efficacy, and pain distribution, on functional disability. The spatial distribution of pain had the greatest impact on treatment trajectory in patients with widespread pain, high pain intensity, and poor coping efficacy; these patients demonstrated greater functional disability compared with patients with localized pain. In addition, patients with widespread pain and poor coping efficacy had the most functional disability across all levels of pain intensity. Patients with localized pain and poor coping efficacy demonstrated initial treatment gains, but evidenced an increase in functional disability at follow-up. DISCUSSION Overall, spatial distribution of pain, coping efficacy, and pain intensity played an important role in patients' response to treatment. Better understanding of these variables could improve treatment response, particularly for the most severely disabled chronic pain patients.

PURPOSE: Panobinostat, an orally bioavailable pan-HDAC inhibitor, has demonstrated potent activity in multiple malignancies, including pediatric brain tumors such as DIPG, with increased activity against H3K27M mutant cell lines. Given limited evidence regarding the CNS penetration of panobinostat, we sought to characterize its BBB penetration in a murine model. METHODS: Panobinostat 15 mg/kg was administered IV to 12 CD-1 female mice. At specified time points, mice were euthanized, blood samples were collected, and brains were removed. LC–MS was performed to quantify panobinostat concentrations. C(max) and AUC were estimated and correlated with previously published pharmacokinetic analyses and reports of IC-50 values in DIPG cell lines. RESULTS: Mean panobinostat plasma concentrations (ng/mL) were 27.3 ± 2.5 at 1 h, 7.56 ± 1.8 at 2 h, 1.48 ± 0.56 at 4 h, and 2.33 ± 1.18 at 7 h. Mean panobinostat brain concentrations (ng/g) were 60.5 ± 6.1 at 1 h, 42.9 ± 5.4 at 2 h, 33.2 ± 6.1 at 4 h, and 28.1 ± 4.3 at 7 h. Brain-to-plasma ratio at 1 h was 2.22 and the brain to plasma AUC ratio was 2.63. Based on the published human pharmacokinetic data, the anticipated C(max) in humans is expected to be significantly higher than the IC-50 identified in DIPG models. CONCLUSION: It is expected that panobinostat would be effective in CNS tumors where the IC-50 is in the low nanomolar range. Thus, our data demonstrate panobinostat crosses the BBB and achieves concentrations above the IC-50 for DIPG and other brain tumors and should be explored further for clinical efficacy.

OBJECTIVE To evaluate outcomes associated with an experiential leadership program (the Veterinary Leadership Experience [VLE]) among participants 1 year after program completion. SAMPLE 157 veterinary students and 61 veterinary professionals who participated in the 2015 or 2016 VLE. PROCEDURES Participants completed various instruments to assess emotional intelligence, psychological flexibility, resilience, and client-communication skills prior to (pretest) and 1 year after (posttest) attending the VLE; pretest and posttest findings were compared for all but client-communication skills, for which only posttest responses were analyzed. An additional posttest instrument assessed the impact that the VLE had on key knowledge areas (ie, self-awareness, self-management, social awareness, relational competence, communication skills, and conflict management skills) and overall impact. RESULTS 1 year after completing the VLE, participants reported that the program had a high impact on all key knowledge areas; the impact on social awareness and overall impact was significantly higher for veterinary students than for veterinary professionals. Veterinary professionals reported a greater increase in emotional intelligence after program completion than did veterinary students. For each assessed client-communication skill, the percentage of veterinary professionals who reported increased confidence in that skill after program completion was lower than the corresponding percentage of veterinary students. Resilience and psychological flexibility scores did not increase after program completion. CONCLUSIONS AND CLINICAL RELEVANCE Assessment of the effectiveness and long-term outcomes of experiential leadership programs is important to understanding whether such programs are having the intended effect. Veterinary students and veterinary professionals who were assessed 1 year after completing the VLE reported improvements in leadership skills foundational to the program.

The purpose of this study was to conduct a long-term, population-based, epidemiologic study of psychiatric disorders in mothers of children with attention-deficit/hyperactivity disorder (ADHD). Subjects included mothers of 306 childhood incident cases of ADHD and mothers of 617 age/gender matched controls from a 1976–1982 birth cohort. Compared to mothers of controls, mothers of children with ADHD were significantly more likely to be diagnosed prior to the child’s birth with a depressive disorder (adjusted odds ratio (aOR), 3.1; 95% confidence interval (CI), 1.3–7.7), an adjustment disorder (aOR, 8.1; 95% CI, 1.7–39.5), or any psychiatric disorder (aOR, 2.5; 95% CI, 1.61–4.7) and were likewise significantly more likely to be diagnosed with a de novo (i.e., first diagnosed after the child’s birth) depressive disorder (adjusted hazard ratio (aHR), 1.7; 95% CI, 1.2–2.4), de novo adjustment disorder (aHR, 2.0; 95% CI, 1.4–2.7), or any de novo psychiatric disorder (aHR, 1.7; 95% CI, 1.4–2.2) during the 21 years after the child’s birth. This study provides an opportunity to study the natural occurrence of psychiatric disorders in mothers of children with ADHD and suggests that the likelihood of having a child with ADHD is associated with maternal psychopathology both before and after the birth. This adds to existing knowledge of maternal psychopathology for children with ADHD and has implications for screening and monitoring. Future research is needed to clarify the role that both genetic and environmental risk factors play in the increased rates of psychopathology in mothers of children with ADHD.

Introduction. Kansas falls consistently below average for adolescentvaccination of meningococcal (MCV), human papillomavirus(HPV), and influenza. Methods. For this study, the members of Kansas Chapter of theAmerican Academy of Pediatrics were emailed a confidential electronicsurvey soliciting their impressions of vaccination in theirpractice. Results. Of 137 providers emailed, 61 (45%) completed the survey.Thirteen providers were excluded as they did not see/vaccinate adolescentsor did not complete the survey. Tetanus, diphtheria, pertussis(Tdap), and MCV vaccines were most commonly up to date with31 (65%) and 20 (42%) respondents reporting greater than 90%immunization rates, respectively. HPV (n = 42, 89%) and influenza(n = 40, 83%) vaccines had refusal rates greater than 25% in mostclinics. Most practices (n = 44, 92%) used internal electronic medicalrecords to track vaccinations, although 29 practices (60%) utilizedthe state immunization information system. Providers requestedvaccine-specific patient education tools, positive media coverage,staffing support, and best-practices workshops to support vaccinationefforts. Conclusion. Kansas providers may not be optimizing availableresources to enhance these rates, such as Web IZ tracking and immunizationreminders. Patient education supplies, specific to HPV andInfluenza vaccination, potentially could increase vaccination rates.KS J Med 2017;10(4):84-87.

We develop a physics-based mathematical model for the signals received from a fixed radar that interrogates a moving target and a single rotating object located in the same range cell. From this ma...

BACKGROUND: The pathophysiology of salt-sensitive hypertension remains uncertain, but may involve microvascular alterations. High-salt intake decreases microvascular density in hypertensive patients, but due to lack of studies in normotensive patients the causal pathway remains unclear. We studied whether high-salt intake decreases sublingual microvascular density in normotensive individuals and assessed the influence of body weight on changes in microvascular density. METHODS: In an open label randomized cross-over trial 18 healthy men were included to study the effect of a 2-week high-salt (>12 g/day) and low-salt (

The role of metabolite-responsive riboswitches in regulating gene expression in bacteria is well known and makes them useful systems for the study of RNA-small molecule interactions. Here, we study the PreQ1 riboswitch system, assessing sixteen diverse PreQ1-derived probes for their ability to selectively modify the class-I PreQ1 riboswitch aptamer covalently. For the most active probe (11), a diazirine-based photocrosslinking analog of PreQ1, X-ray crystallography and gel-based competition assays demonstrated the mode of binding of the ligand to the aptamer, and functional assays demonstrated that the probe retains activity against the full riboswitch. Transcriptome-wide mapping using Chem-CLIP revealed a highly selective interaction between the bacterial aptamer and the probe. In addition, a small number of RNA targets in endogenous human transcripts were found to bind specifically to 11, providing evidence for candidate PreQ1 aptamers in human RNA. This work demonstrates a stark influence of linker chemistry and structure on the ability of molecules to crosslink RNA, reveals that the PreQ1 aptamer/ligand pair are broadly useful for chemical biology applications, and provides insights into how PreQ1, which is similar in structure to guanine, interacts with human RNAs., The small modified nucleotide PreQ1 binds to the PreQ1 riboswitch and regulates gene expression by inducing RNA conformation change. Here the authors design and characterize a specific preQ1-derived probe by x-ray crystallography, mass spectral analysis and transcriptome-wide using Chem-CLIP.

Nausea, vomiting, constipation, and diarrhea are common cancer and cancer therapy adverse effects. Pharmacists are uniquely positioned to optimize patient symptom control and minimize excess use of hospital resources, such as emergency department visits.Michigan Medicine oncology clinical pharmacists have been independently providing patient symptom management through a collaborative drug therapy management (CDTM) program which established guidelines for management of gastrointestinal toxicities (nausea, vomiting, diarrhea, and/or constipation) secondary to a patient's cancer diagnosis or treatment of the cancer. Patients were referred to the pharmacist by the treating oncologist or hematologist.From June 2019 to May 2020, there were a total of 62 patient referrals. Ten of the 62 referrals did not meet the CDTM inclusion criteria, resulting in 52 patients who were managed by the pharmacists. The total number of individual pharmacist visits was 136, with a median of 2.2 (range, 0-11) visits per patient referred. A total of 169 categorized pharmacist interventions were captured. Most interventions (100/169, 59.2%) were related to nausea/vomiting. Diarrhea-related and constipation-related interventions accounted for 10 (5.9%) and 13 (7.7%) of the total interventions, respectively. Most patients (36/52, 69.2%) had a reduction in the severity of their referral diagnosis symptom(s) based on Common Terminology Criteria for Adverse Events grading.The Michigan Medicine Pharmacist CDTM program allowed pharmacists to independently manage gastrointestinal toxicities of patients with cancer and improved patient symptom severity. The CDTM program has the opportunity to improve quality of care.

We report on a long-term optical monitoring of the neutron star X-ray binary Centaurus X-4 performed during the last 13.5 years. This source has been in quiescence since its outburst in 1979. Our monitoring reveals the overall evolution of the accretion disc; we detect short-duration flares, likely originating also in the disc, superimposed with a small-amplitude (< 0.1 mag) ellipsoidal modulation from the companion star due to geometrical effects. A long-term (~2300 days) downward trend, followed by a shorter (~1000 days) upward one, is observed in the disc light curve. Such a rise in the optical has been observed for other X-ray binaries preceding outbursts, as predicted by the disc instability model. For Cen X-4, the rise of the optical flux proceeded for ~3 years, and culminated in a flux increase at all wavelengths (optical-UV-X-rays) at the end of 2020. This increase faded after ~2 weeks, without giving rise to a full outburst. We suggest that the propagation of an inside-out heating front was ignited due to a partial ionization of hydrogen in the inner disc. The propagation might have stalled soon after the ignition due to the increasing surface density in the disc that the front encountered while propagating outwards. The stall was likely eased by the low level irradiation of the outer regions of the large accretion disc, as shown by the slope of the optical/X-ray correlation, suggesting that irradiation does not play a strong role in the optical, compared to other sources of emission., 18 pages, 10 figures, accepted for publication in ApJ

ObjectivesInforming research participants of the results of studies in which they took part is viewed as an ethical imperative. However, there is little guidance in the literature about how to do this. The Fluoxetine Or Control Under Supervision trial randomised 3127 patients with a recent acute stroke to 6 months of fluoxetine or placebo and was published in the Lancet on 5 December 2018. The trial team decided to inform the participants of the results at exactly the same time as the Lancet publication, and also whether they had been allocated fluoxetine or placebo. In this report, we describe how we informed participants of the results.DesignIn the 6-month and 12-month follow-up questionnaires, we invited participants to provide an email address if they wished to be informed of the results of the trial. We re-opened our trial telephone helpline between 5 December 2018 and 31 March 2019.SettingUK stroke services.Participants3127 participants were randomised. 2847 returned 6-month follow-up forms and 2703 returned 12-month follow-up forms; the remaining participants had died (380), withdrawn consent or did not respond.ResultsOf those returning follow-up questionnaires, a total of 1845 email addresses were provided and a further 50 people requested results to be sent by post. Results were sent to all email and postal addresses provided; 309 emails were returned unrecognised. Seventeen people replied, of whom three called the helpline and the rest responded by email.ConclusionIt is feasible to disseminate results of large trials to research participants, though only around 60% of those randomised wanted to receive the results. The system we developed was efficient and required very little resource, and could be replicated by trialists in the future.Trial registration numberISRCTN83290762; Post-results.

Early life adversity has long-term detrimental effects on physical health. Although biological, behavioral, and social factors have been explored as intermediate mechanisms, little research has explored psychosocial factors as potential mediators. This study examined whether purpose in life longitudinally mediates the relationship between childhood adversity and two measures of adult health. Data were obtained from 3,871 participants in the Midlife in the United States (MIDUS) study. We tested a longitudinal mediation model from childhood adversity to adult health via purpose in life, controlling for baseline measures of health. Results indicated that childhood adversity is associated with poorer adult health through direct and mediated paths. Childhood adversity may restrict individuals' sense of purpose in life, and reduced purpose in life is subsequently associated with poorer subjective health and increased likelihood of functional limitations. The findings of this study can be used to inform the development of psychosocial and therapeutic intervention programs and services for adults with a history of childhood adversity.

The original version of this review article unfortunately contained a mistake in the author group section.

The efficacy of family-based treatment (FBT) in outpatient settings has led to efforts to incorporate FBT principles into higher levels of care. The present study examined predictors of improvement in an FBT-based partial hospitalization program/intensive outpatient program (PHP/IOP) as measured by the Eating Disorder Examination-Questionnaire. Participants were 113 patients with anorexia nervosa (AN) or eating disorder not otherwise specified (EDNOS) consecutively participating in an FBT-based PHP/IOP. Multilevel modeling was used to investigate predictors for adolescents and young adults separately. Predictors considered included illness duration, previous hospitalization, hospitalization immediately prior to treatment, previous outpatient therapy, hospitalization during treatment, diagnosis, gaining 4 pounds in 4 weeks, and family status as time-invariant variables. Time-varying variables considered included depression symptoms and mothers'/fathers' ratings of parental self-efficacy and expressed emotion. For adolescents, depression by time and diagnosis by time interactions were statistically significant. At all levels of depression, adolescent patients with AN demonstrated greater reductions in eating disorder symptoms compared to patients with EDNOS. For young adults, depression and gaining 4 pounds in 4 weeks were significant predictors. The relationships for young adults were curvilinear such that, while lower eating disorder symptoms were found during treatment, these gains were not maintained at follow up.