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An increasing body of evidence supports the use of family-based treatment (FBT) in medically stable outpatient presentations of adolescent anorexia nervosa, although there is relatively less research on adapting evidence-based treatment approaches in more intensive levels of patient care. The integration of FBT, which centrally leverages parental involvement in more intensive levels of care which typically require greater clinical management, requires careful consideration. We provide an overview of several key practical and theoretical considerations when adjusting the delivery of FBT across more intensive levels of patient care, providing clinical guidelines for the delivery of FBT while ensuring fidelity to the core theoretical tenets. Implications for clinical practice and future research are discussed.

Adolescent bulimia nervosa (BN) remains relatively understudied, and the complex interaction between core eating psychopathology and emotional regulation difficulties provides ongoing challenges for full symptom remission. In an open pilot trial, we aimed to investigate the efficacy of a program integrating family-based treatment (FBT) and dialectical behavior therapy (DBT) in treating adolescent BN, without exclusion criteria. Participants were 35 adolescents who underwent partial hospital treatment for BN, and outcomes included measures of core BN pathology and emotional regulation difficulties, as well as parental measures of self-efficacy, completed at intake and discharge. Results indicate significant improvements in overall eating disorder pathology, t(68) = 4.52, p =.002, and in core BN symptoms, including objective binge episodes, t(68) = 2.01, p =.041, and self-induced vomiting, t(68) = 2.90, p =.005. Results also illustrated a significant increase in parental efficacy throughout the course of treatment, t(20) =.081, p =.001, although no global improvement in difficulties in emotion regulation was noted, t(68) = 1.12, p =.285. These preliminary findings support the utility of this integration of FBT and DBT, although raise interesting questions as to the mechanism of symptom remission.

Dialectical behavior therapy (DBT) and family-based treatment (FBT) are two evidence-based interventions that have been applied in the treatment of bulimia nervosa (BN) in adolescents. While DBT focuses on providing skills for coping with emotion dysregulation that often co-occurs with BN, FBT targets the normalization of eating patterns. The purpose of the current article is to introduce an integration of both treatments to provide a more comprehensive approach that targets the full scope of the disorder. We provide a review of the conceptual similarities and differences between FBT-BN and DBT along with strategies to guide a blended treatment approach. Given the strengths and limitations of either independent treatment, DBT and FBT-BN complement one another and together can address the range of symptoms and behaviors typically seen in adolescent BN.

The purpose of this study was to compare the echocardiographic Doppler blood pressure and heart rate effects of 1:1 thiopental/propofol with thiopental and propofol, when used as anesthesia-induction agents. Seven healthy dogs (six Beagles and one Pembroke Welsh Corgi), ranging in age from 1 to 9 years and weighing 14.2 ± 2.4 kg (mean ± SD), were used during the study. In a cross-over study design with a minimum drug interval of 3 days, each dog received propofol, thiopental, or a mixture of propofol–thiopental IV until each dog received all the three anesthetic agents. An initial dose (propofol 4.9 ± 0.8 mg kg-1 ; thiopental 12.9 ± 2.4 mg kg-1 ; propofol–thiopental 2.3 ± 0.3 mg kg-1 (P)-5.7 ± 0.8 mg kg-1 (T)) of each anesthetic agent was titrated IV until intubation was accomplished. Echocardiographic Doppler blood pressure and heart rate variables were recorded prior to anesthesia and at 1, 5, and 10 minutes after induction of anesthesia. anova and the Bonferroni's t -test were used to evaluate the groups for differences. Alpha was <0.05. There was no significant effect of treatment on systolic or diastolic ventricular wall thickness, septal thickness, left atrial diameter, or systolic left ventricular diameter. There was a tendency for diastolic left ventricular diameter to decrease over time. There was a tendency for heart rate to increase with a significant difference at the 10-minute time period between propofol (109 ± 26 beats minute-1 ) and thiopental (129 ± 23 beats minute-1 ). At the 10-minute recording period, heart rate following the propofol/thiopental mixture (110 ± 34 beats minute-1 ) was closer to that following propofol than to that following thiopental. With all induction agents, indirect blood pressure tended to decrease over time (p = 0.005); however, there was no difference between the groups. The changes observed were not considered to be of clinical significance. The propofol/thiopental mixture produces similar changes in echocardiographic variables when compared to propofol or thiopental, and could be substituted for propofol for induction of anesthesia in dogs. [ABSTRACT FROM AUTHOR]

Existing literature on the effects of borderline personality disorder (BPD) and eating disorder (ED) comorbidity in terms of clinical presentation and treatment outcome has been limited and inconclusive. The present study examined whether clients with EDs and varying levels of BPD symptoms presented with more severe ED symptoms at admission, and whether they responded to dialectical behavior therapy (DBT)-based treatment. Participants ( N = 176) were adults in a DBT-based partial hospitalization program for EDs at an academic medical center. Participants completed self-report measures at admission, 1-month postadmission, discharge, and 6-month follow-up. Results suggested that patients with elevated BPD symptoms at admission had greater ED symptoms during treatment, evidenced by small to moderate effect sizes. However, patients with high BPD symptoms demonstrated steeper declines in binge eating, fasting, and parasuicidal behavior early during treatment compared to patients with low BPD symptoms. Individuals with high BPD symptoms at admission (i.e., probable BPD diagnosis) were as likely to meet remission criteria and relapse as individuals with low BPD symptoms, though this null finding may be influenced by small cell sizes. Our findings also suggest that DBT skills use does not predict changes in symptoms. In sum, our findings suggest that while clients with higher BPD symptoms may improve during DBT-based partial hospitalization, their ED symptoms may remain more severe. Future studies are needed to determine whether adjunctive treatments improve outcomes for clients with EDs and comorbid BPD symptoms in DBT programs and whether skills use quality is a better predictor of ED symptom changes. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Background: Research on hypermobile Ehlers-Danlos syndrome and hypermobility spectrum disorder (hEDS/HSD) has described its natural history and clinical course in children, adolescents, and young to middle-aged adults. However, more research is needed on the clinical trajectory of hEDS/HSD into older age. Therefore, clinicians, including nurse practitioners, know little about identifying older adults with undiagnosed hEDS/HSD., Objective: This review sought to identify studies regarding aging in hEDS/HSD., Data Sources: This scoping review included PubMed, Cumulative Index to Nursing and Allied Health Literature, and Scopus and found 15 studies that mentioned age or aging on the symptoms and health-related quality of life., Conclusions: No study had a stated aim regarding aging in hEDS/HSD, but all studies corroborated earlier natural history studies describing the age-related trajectory of manifestations in younger people. Studies found that symptom progression was heterogeneous, multisystemic, and unpredictable. Studies also noted prolonged diagnosis delays and long symptom duration, but the impact of these factors on outcomes was unclear. The high variability in patient outcomes precludes the prediction of outcomes based on the included studies. The clinical impact of aging on hEDS/HSD remains mostly speculative., Implications for Practice: Nurse practitioners, especially those in primary care, should consider that older adults presenting with multimorbidity may have undiagnosed hEDS/HSD. More research is needed to identify symptom patterns and clinical history that may suggest an underlying connective tissue disorder., Competing Interests: Competing interests: The authors report no conflicts of interest., (Copyright © 2023 American Association of Nurse Practitioners.)

Introduction: Hypermobile Ehlers-Danlos syndrome and hypermobility spectrum disorders cause joint instability, chronic pain, fatigue and progressive multisystemic dysfunction, increasing symptom burden and decreasing quality of life. Researchers know little about how these disorders progress in women as they age., Objective: This research aimed to determine the feasibility of an internet-based study to understand the clinical characteristics, symptom burden and health-related quality of life in older women with symptomatic hypermobility disorders., Methods: This cross-sectional, internet-based survey studied recruitment methods, suitability and usability of survey instruments and obtained baseline data on women aged 50 and older with hEDS/HSD. Researchers recruited participants from a Facebook group for older adults with Ehlers-Danlos syndrome. Outcome measures included health history, the Multidimensional Health Assessment Questionnaire and the RAND Short Form 36 health survey., Results: Researchers recruited 32 participants from a single Facebook group within 2 weeks. Nearly all participants were satisfied with the survey length, clarity and navigation, with 10 participants providing free-text recommendations for survey improvement. The survey suggests a high symptom burden and poor quality of life in older women with hEDS/HSD., Conclusion: The results support the feasibility and importance of a future internet-based comprehensive study about hEDS/HSD in older women., (© 2023 John Wiley & Sons Ltd.)

Background: While implantation of an inflatable penile prosthesis (IPP) is commonly performed via infrapubic or penoscrotal approaches, the subcoronal (SC) approach for IPP implantation may safely and reliably allow for additional reconstructive procedures through a single incision., Aim: The aim of this study is to report outcomes, including complications, of the SC approach and to determine common characteristics of patients undergoing the SC approach., Methods: A retrospective chart review from May 11, 2012, to January 31, 2022, was performed at a single, tertiary care institution to identify patients with IPP implantation via the SC approach., Outcomes: Postoperative information was reviewed and extracted from all clinic notes available following the date of IPP implantation in the electronic medical record, detailing any complications including wound complications, need for revision or removal, device malfunction, and infections., Results: Sixty-six patients had IPP implantation via the SC approach. Median follow-up duration was 29.4 (interquartile range 14.9-50.1) months. One (1.8%) patient had a simple wound complication. Two (3.6%) experienced postoperative infection of the prosthesis, which resulted in explantation of the device. One of these infected prostheses later experienced partial glans necrosis. Revision for mechanical failure or unsatisfactory cosmetic result was performed in 3 (7.3%) IPPs placed via a SC incision., Clinical Implications: The SC approach for implantation of IPP is safe and feasible with low complication and revision rates. It offers urologists an alternative to the classic infrapubic and penoscrotal approaches, both of which would require a second incision for additional reconstructive procedures required to adequately address deformities associated with severe Peyronie's disease. Therefore, urologists who treat these specialized populations of men may benefit from having the SC approach in their array of techniques for IPP implantation., Strengths and Limitations: The limitations of this study include its retrospective nature, risk of selection bias, lack of comparison groups, and sample size. This study reports on early experience with the SC approach performed by a single high-volume reconstructive surgeon, who treats a specialized population of patients requiring complex repair during implantation of an IPP, particularly those with Peyronie's disease., Conclusion: The SC incision for IPP implantation has low rates of complications and remains our approach of choice for IPP implantation in patients with severe Peyronie's disease, including curvatures >60°, severe indentation with hinge, and grade 3 calcification, which are unlikely to respond adequately to manual modeling alone., (© Published by Oxford University Press on behalf of The International Society of Sexual Medicine 2023.)

Lay Abstract: Autism spectrum disorder is a developmental disability affecting individuals across their entire lifespan. Autistic individuals have differences from nonautistic people (sometimes called allistic or neurotypical people) in social skills, communication, and atypical interests and/or repetitive behaviors. Applied behavior analysis is one of the first and most common interventions recommended for autistic children. However, autistic individuals argue that applied behavior analysis damages their mental health and treats them as though they are a problem to be fixed. This study examined the experiences of seven autistic individuals who received applied behavior analysis interventions as children to understand what autistic adults think about their applied behavior analysis interventions, how they feel about the applied behavior analysis interventions they received, and what recommendations autistic adults have for the future of applied behavior analysis. The findings include: Autistic adults remember traumatic events from applied behavior analysis, do not believe that they should be made to behave like their peers, gained some benefits but suffered significant negative long-term consequences, believe that applied behavior analysis is an unethical intervention, and recommend that applied behavior analysis practitioners listen to autistic people and consider using interventions in place of applied behavior analysis.

Background: Gold-standard psychological and pharmacological treatments for bulimic-spectrum eating disorders only result in remission for around 50% of patients; patients with affective lability and impulsivity represent a subgroup with particularly poor outcomes. Both dialectical behavior therapy (DBT), a treatment for emotion dysregulation, and lamotrigine, a mood stabilizer, have demonstrated promise for targeting affective lability and impulsivity; however, data exploring the combination of these interventions remain limited., Objective: We followed a group of women with recurrent dysregulated eating behaviors (N = 62) throughout intensive DBT treatment and compared the symptom trajectory of those prescribed lamotrigine (n = 28) and those who were not (n = 34)., Method: Participants completed surveys every 2 weeks throughout treatment., Results: Group analyses suggested that all participants self-reported decreases in emotional reactivity, negative urgency, and symptoms of borderline personality disorder (BPD). The lamotrigine group reported greater elevations in BPD symptoms at baseline, but demonstrated steeper decreases in emotion and behavioral dysregulation than the non-matched comparison group. Within-subject analyses suggested that within the lamotrigine group, subjects reported greater decreases in symptoms following prescription of lamotrigine., Conclusions: Findings provide initial data suggesting that lamotrigine could be useful as an adjunctive treatment for patients with affective lability and impulsivity., Level of Evidence: IV, time series without randomization., (© 2022. The Author(s).)

Purpose: Adults with bulimia nervosa (BN) and co-occurring emotional dysregulation and multiple impulsive behaviors are less responsive to existing interventions. Initial data suggest that the combination of Dialectical Behavior Therapy (DBT) and a mood stabilizer, lamotrigine, significantly reduces symptoms of affective and behavioral dysregulation in these patients. Identifying candidate neurobiological mechanisms of change for this novel treatment combination may help guide future randomized controlled trials and inform new and targeted treatment development. Here, we examined neurocognitive and symptom changes in a female patient with BN and severe affective and behavioral dysregulation who received DBT and lamotrigine., Methods: Go/no-go task performance data and resting-state functional MRI scans were acquired before the initiation of lamotrigine (after 6 weeks in an intensive DBT program), and again after reaching and maintaining a stable dose of lamotrigine. The patient completed a battery of symptom measures biweekly for 18 weeks over the course of treatment., Results: After lamotrigine initiation, the patient made fewer errors on a response inhibition task and showed increased and new connectivity within frontoparietal and frontolimbic networks involved in behavioral and affective control. Accompanying this symptom improvement, the patient reported marked reductions in bulimic symptoms, behavioral dysregulation, and reactivity to negative affect, along with increases in DBT skills use., Conclusion: Improved response inhibition and cognitive control network connectivity should be further investigated as neurocognitive mechanisms of change with combined DBT and lamotrigine for eating disorders. Longitudinal, controlled trials integrating neuroimaging and symptom measures are needed to fully evaluate the effects of this treatment., Level of Evidence: IV: Evidence obtained from multiple time series with or without the intervention, such as case studies., (© 2021. The Author(s).)

Lung cancer is the commonest cause of cancer deaths worldwide. Although strongly associated with smoking, predisposition to lung cancer is also heritable, with multiple common risk variants identified. Rarely, dominantly inherited non-small-cell lung cancer (NSCLC) has been reported due to somatic mutations in EGFR/ErbB1 and ERBB2. Germline exome sequencing was performed in a multi-generation family with autosomal dominant NSCLC, including an affected child. Tumour samples were also sequenced. Full-length wild-type (wtErbB3) and mutant ERBB3 (mutErbB3) constructs were transfected into HeLa cells. Protein expression, stability, and subcellular localization were assessed, and cellular proliferation, pAkt/Akt and pERK levels determined. A novel germline variant in ERBB3 (c.1946 T > G: p.Iso649Arg), coding for receptor tyrosine-protein kinase erbB-3 (ErbB3), was identified, with appropriate segregation. There was no loss-of-heterozygosity in tumour samples. Both wtErbB3 and mutErbB3 were stably expressed. MutErbB3-transfected cells demonstrated an increased ratio of the 80 kDa form (which enhances proliferation) compared with the full-length (180 kDa) form. MutErbB3 and wtErbB3 had similar punctate cytoplasmic localization pre- and post-epidermal growth factor stimulation; however, epidermal growth factor receptor (EGFR) levels decreased faster post-stimulation in mutErbB3-transfected cells, suggesting more rapid processing of the mutErbB3/EGFR heterodimer. Cellular proliferation was increased in mutErbB3-transfected cells compared with wtErbB3 transfection. MutErbB3-transfected cells also showed decreased pAkt/tAkt ratios and increased pERK/tERK 30 min post-stimulation compared with wtErbB3 transfection, demonstrating altered signalling pathway activation. Cumulatively, these results support this mutation as tumorogenic. This is the first reported family with a germline ERBB3 mutation causing heritable NSCLC, furthering understanding of the ErbB family pathway in oncogenesis., (© The Author(s) 2021. Published by Oxford University Press.)

Background: Researchers have identified lengthy diagnosis delays in patients with hypermobile Ehlers-Danlos syndrome and hypermobility spectrum disorders (hEDS/HSD), but the reason for these delays is unclear., Objective: This review seeks to synthesize the existing qualitative research about hEDS/HSD to understand the reasons for diagnosis delay., Data Sources: We searched PubMed, Scopus, CINAHL, Google Scholar, and Dissertations and Theses databases for all qualitative studies about hEDS/HSD that mentioned the diagnosis process. A total of 283 studies were retrieved, from which we identified 13 studies to include in this synthesis., Conclusions: The reviewers identified and organized diagnosis delay themes under four overarching categories: disease, patient, provider, and system. Disease factors included the nature of the symptoms and lack of a confirmatory test. Patient factors included psychological and emotional responses, seeing multiple providers, and receiving multiple diagnoses. Provider factors related to limited knowledge and attitudes. System factors included silo-based health care systems and bureaucratic barriers., Implications for Practice: Diagnosis delays result from complex, overlapping, and interacting factors. Nurse practitioners have a critical role in improving care and reducing diagnosis delays in patients with hEDS/HSD. Further research is needed to understand the causes and consequences of diagnosis delays in hEDS/HSD., Competing Interests: Competing interests: The authors report no conflicts of interest., (Copyright © 2021 American Association of Nurse Practitioners.)

Objective: We sought to test the hypothesis that Polygenic Risk Scores (PRSs) have strong capacity to discriminate cases of ankylosing spondylitis (AS) from healthy controls and individuals in the community with chronic back pain., Methods: PRSs were developed and validated in individuals of European and East Asian ethnicity, using data from genome-wide association studies in 15 585 AS cases and 20 452 controls. The discriminatory values of PRSs in these populations were compared with other widely used diagnostic tests, including C-reactive protein (CRP), HLA-B27 and sacroiliac MRI., Results: In people of European descent, PRS had high discriminatory capacity with area under the curve (AUC) in receiver operator characteristic analysis of 0.924. This was significantly better than for HLA-B27 testing alone (AUC=0.869), MRI (AUC=0.885) or C-reactive protein (AUC=0.700). PRS developed and validated in individuals of East Asian descent performed similarly (AUC=0.948). Assuming a prior probability of AS of 10% such as in patients with chronic back pain under 45 years of age, compared with HLA-B27 testing alone, PRS provides higher positive values for 35% of patients and negative predictive values for 67.5% of patients. For PRS, in people of European descent, the maximum positive predictive value was 78.2% and negative predictive value was 100%, whereas for HLA-B27, these values were 51.9% and 97.9%, respectively., Conclusions: PRS have higher discriminatory capacity for AS than CRP, sacroiliac MRI or HLA-B27 status alone. For optimal performance, PRS should be developed for use in the specific ethnic groups to which they are to be applied., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Previous research supports the relevance of early symptom change in eating disorder (ED) treatment; however, few studies have distinguished early weight change from early change in ED psychopathology, particularly in higher levels of care. Thus, the present study examined whether early change in weight and ED psychopathology predicted outcome for adolescents with anorexia nervosa (AN) in a partial hospitalization program., Method: Adolescents with AN (n = 99) completed assessments at admission, 1-month after treatment admission, discharge, and 6-month follow-up., Results: Higher admission percent expected body weight (%EBW), greater early change in %EBW, longer duration of treatment, shorter length of illness, and earlier age of onset predicted greater change in %EBW at discharge, but not follow-up. Greater ED psychopathology at admission and greater early change in ED psychopathology predicted later change in ED symptoms at discharge, but not follow-up. Neither early change in %EBW nor ED psychopathology predicted likelihood of remission at discharge and follow-up., Discussion: Results support the importance of early change in predicting later change in the same ED outcome variables and suggest that early change in both %EBW and ED psychopathology in adolescents may be an important area for future research., (© 2020 Wiley Periodicals LLC.)

Background: The human enthesis conventional T cells are poorly characterised., Objectives: To study the biology of the conventional T cells in human enthesis., Methods: CD4+ and CD8+ T cells were investigated in 25 enthesis samples using immunofluorescence, cytometrically, bulk RNAseq and quantitative real-time PCR following anti-CD3/CD28 bead stimulation to determine interleukin (IL)-17A and tumour necrosis factor (TNF) levels. T-cell receptor (TCR) repertoires were characterised and a search for putative T-cell reactivity was carried out using TCR3 database. The impact of pharmacological antagonism with retinoic acid receptor-related orphan nuclear receptor gamma t inhibitor (RORγti), methotrexate and phosphodiesterase type 4 inhibitor (PDE4i) was investigated., Results: Immunofluorescence and cytometry suggested entheseal resident CD4+ and CD8+ T cells with a resident memory phenotype (CD69+/CD45RA-) and tissue residency gene transcripts (higher NR4A1/AhR and lower KLF2/T-bet transcripts). Both CD4+ and CD8+ T cells showed increased expression of immunomodulatory genes including IL-10 and TGF-β compared with peripheral blood T cells with entheseal CD8+ T cells having higher CD103, CD49a and lower SIPR1 transcript that matched CD4+ T cells. Following stimulation, CD4+ T cells produced more TNF than CD8+ T cells and IL-17A was produced exclusively by CD4+ T cells. RNAseq suggested both Cytomegalovirus and influenza A virus entheseal resident T-cell clonotype reactivity. TNF and IL-17A production from CD4+ T cells was effectively inhibited by PDE4i, while RORγti only reduced IL-17A secretion., Conclusions: Healthy human entheseal CD4+ and CD8+ T cells exhibit regulatory characteristics and are predicted to exhibit antiviral reactivity with CD8+ T cells expressing higher levels of transcripts suggestive of tissue residency. Inducible IL-17A and TNF production can be robustly inhibited in vitro., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Emotion regulation deficits are associated with eating disorder (ED) symptoms, regardless of eating disorder diagnosis. Thus, recent treatment approaches for EDs, such as dialectical behavior therapy (DBT), have focused on teaching patients skills to better regulate emotions. The present study examined changes in emotion regulation among adult patients with EDs during DBT-oriented partial hospital treatment, and at follow-up (M[SD] = 309.58[144.59] days from discharge). Exploratory analyses examined associations between changes in emotion regulation and ED symptoms. Patients with anorexia nervosa, restricting (AN-R, n = 77), and binge-eating/purging subtype (AN-BP, n = 46), or bulimia nervosa (BN, n = 118) completed the Difficulties in Emotion Regulation Scale (DERS) at admission, discharge, and follow-up. Patients with BN demonstrated significant improvements across all facets of emotion dysregulation from admission to discharge and maintained improvements at follow-up. Although patients with AN-BP demonstrated statistically significant improvements on overall emotion regulation, impulsivity, and acceptance, awareness, and clarity of emotions, from admission to discharge, these improvements were not significant at follow-up. Patients with AN-R demonstrated statistically significant improvements on overall emotion dysregulation from treatment admission to discharge. Changes in emotion regulation were moderately correlated with changes in ED symptoms over time. Results support different trajectories of emotion regulation symptom change in DBT-oriented partial hospital treatment across ED diagnoses, with patients with BN demonstrating the most consistent significant improvements., (Copyright © 2019. Published by Elsevier Ltd.)

Over the past several decades, Dialectical Behavior Therapy (DBT) has been adapted for a range of presenting problems related to emotion dysregulation. Considerable enthusiasm exists regarding the use of DBT for treating eating disorders; however, to date, there have been no reviews summarizing empirical efforts to adapt DBT for eating disorders in youth. Accordingly, in the present narrative review, we provide a comprehensive summary of existing work testing DBT for adolescent eating disorders. First, we briefly review existing work applying DBT to eating disorders in adults and general adolescent samples. We then review research focused specifically on the use of DBT for adolescent eating disorders, including both those studies applying DBT as the primary treatment and investigations of DBT as an adjunctive treatment. Overall, initial results for DBT-based approaches are promising. However, rigorous empirical work testing DBT for treating adolescent eating disorders remains limited; the majority of existing research is comprised of case series and small-scale studies. Therefore, we close with specific recommendations for future research testing this approach.

Despite initial data suggesting positive treatment outcomes for adolescent eating disorder day-hospital programmes (DHPs), existing studies have included limited follow-up, small samples, and a focus on restricting-type eating disorders. To address these gaps, we explored naturalistic outcomes for an adolescent eating disorders DHP. Adolescent participants (N = 265) completed measurements at treatment admission, discharge (n = 170), and various lengths of follow-up (n = 126; M follow up = 278.87 days). Results from multilevel models indicated significant increases in body weight for the anorexia nervosa group throughout treatment and maintenance of increased body weight from discharge to follow-up. In bulimic spectrum disorders, binge eating and purging significantly decreased from intake to discharge and did not change from discharge to follow-up. Across the entire sample, eating disorder symptoms decreased from intake to discharge and did not change from discharge to follow-up. Further, anxiety and depression decreased over the course of treatment and continued to decrease over the follow-up period. The current investigation represents the first study to explore longitudinal DHP outcomes within adolescent bulimic spectrum eating disorders. Our findings also highlight many challenges inherent in conducting naturalistic research; it is critical that the field continue to develop solutions to the barriers inherent in conducting longitudinal research on eating disorder treatment., (© 2020 John Wiley & Sons, Ltd and Eating Disorders Association.)

Background: Falls and fall-related injuries remain an ongoing and serious health problem in older adults. Many clinical and environmental factors have been implicated in falls and recurrent falls, including sleep disturbances, sensory deficits, balance problems, incontinence, comorbid conditions, and certain categories of medications. We undertook this study to determine if there was an association between these factors and falls or recurrent falls in older adult residents of an aging in place community., Methods: Our retrospective case-control study compared residents who did and did not fall in an aging in place community, as well as those who experienced recurrent versus single falls in a single year., Results: A total of 50 residents met the criteria for inclusion in this study, with 30 participants (60%) having experienced one or more falls during the observation period. Of the 30 participants who fell, 21 (70%) experienced more than one fall in a single year. Variables associated with falls included marital status and bowel incontinence; variables associated with recurrent falls included self-reported sleep difficulty, balance with sitting to standing and surface-to-surface transfer, use of a walker, and use of antidepressant medications., Discussion: Our study supports the existing nursing research that falls, and recurrent falls are the result of multiple, interrelated factors. Further research is needed into preventative measures for both falls and recurrent falls, particularly in the context of aging in place., Competing Interests: Declaration of competing interest The authors declare no potential competing interests in the research, authorship or publication of this article., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Immunofluorescence and fluorescence in situ hybridization (FISH) can be used to locate specific proteins and DNA sequences, respectively, in chromosomes by light microscopy. Here we describe sequential use of these techniques on spreads of maize synaptonemal complexes (SCs) to determine whether crossing over can occur in knob heterochromatin. We used antibodies to AFD1, an SC protein, and MLH1, a class I (interference-sensitive) crossover protein found in most recombination nodules (RNs) to identify crossovers (COs) along SCs. Next, we used FISH to localize a 180 bp knob-specific tandem repeat. Combining immunofluorescence and FISH images of the same SC spreads showed that heterochromatic knobs do not prohibit class I COs. This technique is broadly applicable to investigations of plant prophase I chromosomes where meiotic recombination takes place.

Background: Maturity-onset diabetes of the young (MODY) is caused by autosomal dominant mutations in one of 13 confirmed genes. Estimates of MODY prevalence vary widely, as genetic screening is usually restricted based on clinical features, even in population studies. We aimed to determine prevalence of MODY variants in a large and unselected pediatric diabetes cohort., Methods: MODY variants were assessed using massively parallel sequencing in the population-based diabetes cohort (n = 1363) of the sole tertiary pediatric diabetes service for Western Australia (population 2.6 million). All individuals were screened, irrespective of clinical features. MODY variants were also assessed in a control cohort (n = 993)., Results: DNA and signed consent were available for 821 children. Seventeen children had pathogenic/likely pathogenic variants in MODY genes, two diagnosed with type 2 diabetes, four diagnosed with antibody-negative type 1 diabetes (T1DM), three diagnosed with antibody-positive T1DM, and eight previously diagnosed with MODY. Prevalence of MODY variants in the sequenced cohort was 2.1%, compared to 0.3% of controls., Conclusions: This is the first comprehensive study of MODY variants in an unselected population-based pediatric diabetes cohort. The observed prevalence, increasing access to rapid and affordable genetic screening, and significant clinical implications suggest that genetic screening for MODY could be considered for all children with diabetes, irrespective of other clinical features., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: Although much empirical attention has been devoted to emotion regulation (ER) in individuals with eating disorders, little is known about ER across a wide age range and among different ED subtypes. The current study sought to examine ER in a sample of eating disorder patients., Method: A total of 364 adults and adolescents with anorexia nervosa restricting subtype (AN-R), anorexia nervosa binge/purge subtype (AN-BP), or bulimia nervosa (BN) were assessed with the Difficulties in Emotion Regulation Scale (DERS)., Results: Older ages were associated with higher DERS total, nonacceptance, goals, and impulsivity scores. When controlling for age, patients with BN and AN-BP had higher overall DERS scores than those with AN, and there were some differences among diagnostic subtypes on specific facets of ER., Conclusions: These results indicate that treatments for emotion dysregulation may be applied across eating disorder diagnoses and ages, and inform how these strategies apply to different diagnostic groups., (© 2018 Wiley Periodicals, Inc.)

Background: To assess the utility of whole-exome sequencing (WES) for mutation detection in maturity-onset diabetes of the young (MODY) and congenital hyperinsulinism (CHI). MODY and CHI are the two commonest monogenic disorders of glucose-regulated insulin secretion in childhood, with 13 causative genes known for MODY and 10 causative genes identified for CHI. The large number of potential genes makes comprehensive screening using traditional methods expensive and time-consuming., Methods: Ten subjects with MODY and five with CHI with known mutations underwent WES using two different exome capture kits (Nimblegen SeqCap EZ Human v3.0 Exome Enrichment Kit, Nextera Rapid Capture Exome Kit). Analysis was blinded to previously identified mutations, and included assessment for large deletions. The target capture of five exome capture technologies was also analyzed using sequencing data from >2800 unrelated samples., Results: Four of five MODY mutations were identified using Nimblegen (including a large deletion in HNF1B). Although targeted, one mutation (in INS) had insufficient coverage for detection. Eleven of eleven mutations (six MODY, five CHI) were identified using Nextera Rapid (including the previously missed mutation). On reconciliation, all mutations concorded with previous data and no additional variants in MODY genes were detected. There were marked differences in the performance of the capture technologies., Conclusions: WES can be useful for screening for MODY/CHI mutations, detecting both point mutations and large deletions. However, capture technologies require careful selection., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To reduce door-to-angiographic reperfusion (DTR) time to 120 minutes for patients presenting with acute ischemic stroke attributed to anterior circulation large-vessel occlusion amenable to endovascular mechanical thrombectomy., Patients and Methods: Patients treated with mechanical thrombectomy before (April 10, 2015, through April 11, 2016) and after (April 12, 2016, through May 10, 2017) implementation of a multitiered notification system were studied. Lean process mapping was used to assess inefficiencies with multidisciplinary triage. A 3-tiered paging platform, which rapidly alerts essential personnel of the acute ischemic stroke team at advancing decision points, was introduced., Results: Sixty-two patients were analyzed before and after implementation (34 vs 28, respectively). Following intervention, DTR time was reduced by 43 minutes (mean DTR, 170 minutes vs 127 minutes; P =.02). At 90-day follow up, 5 of the 28 patients in the postintervention cohort (19%) had excellent neurologic outcomes, defined as a modified Rankin Scale score of 0, compared to 0 of 34 (0%) in the preintervention cohort ( P =.89). Reductions were also seen in the length of stay on the neurocritical care service (mean, 6 vs 3 days; P =.006), and total hospital charges for combined groups (mean, $100,083 vs $161,458; P <.001)., Conclusion: The multitiered notification system was a feasible solution for improving DTR within our institution, resulting in reductions of overall DTR time, neurocritical care service length of stay, and total hospital charges.

Partial hospital programmes (PHPs) have demonstrated efficacy in the treatment of eating disorders (EDs); however, few programmes have examined long-term outcomes across diagnoses, including subtypes of anorexia nervosa (AN). The present study examined the effectiveness of PHP for adult patients (n = 243) with AN-restricting subtype (n = 79), AN binge/purge subtype (n = 46), and bulimia nervosa (n = 118). These patients tended to have long-standing courses of illness (43%, illness duration >7 years) and high levels of psychiatric comorbidity (92.2%). Patients completed questionnaires at admission, discharge, and follow-up, M (SD) = 11.50 months (5.29). Through follow-up, all diagnoses demonstrated significant improvements in weight, ED psychopathology, and comorbid symptoms, with some exceptions for the AN binge/purge group. In exploratory analyses, 49% of patients met criteria for full or partial remission at discharge and 37% at follow-up. Results provide support for the effectiveness of PHP in improving ED outcomes in a severe sample through longer-term follow-up., (Copyright © 2018 John Wiley & Sons, Ltd and Eating Disorders Association.)

Research supports that anorexia nervosa-restricting subtype (AN-R) and bulimia nervosa (BN) are associated with emotion regulation difficulties and alexithymia. However, the impact of diagnosis on the relationship between these constructs is less well understood. The purpose of the present study was to examine whether eating disorder diagnosis moderated the association between admission alexithymia and emotion regulation through discharge. Adult patients with AN-R (n = 54) and BN (n = 60) completed assessments at treatment admission and discharge from a partial hospital program. Eating disorder diagnosis moderated the association between admission alexithymia levels and change in global emotion dysregulation, impulse control difficulties and access to emotion regulation strategies. At higher levels of admission alexithymia, there were no differences between AN-R and BN on emotion dysregulation, whereas at lower levels of alexithymia, AN-R patients demonstrated lower levels of emotion dysregulation. Results imply that difficulties with alexithymia appear to have a greater impact on emotion dysregulation for AN-R patients. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association., (Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.)

Emotional eating is associated with obesity and disordered eating in adolescents, and thus, is an important target for treatment. We developed a program called PEER (Preventing Emotional Eating Routines), which incorporates emotion regulation skills with behavioral weight loss and parenting techniques for adolescents who are overweight or obese (OW/OB) and their parent. This open label trial evaluated the feasibility, acceptability, and initial efficacy of the PEER program. Thirty adolescents who were OW/OB (86.7% female; mean age = 14.6 years (SD = 1.2); Body Mass Index (BMI) = 34.0 kg/m 2 (SD = 5.6); 33.3% White non-Hispanic) and their parent (66.7% biological mother) participated in a 4-month treatment and 3-month follow-up. The PEER program was well accepted. Initial efficacy showed significant decreases in emotional eating, and there were trends towards weight loss and a decrease in emotion dysregulation. This trial provides preliminary evidence for the feasibility, acceptability, and initial efficacy of the PEER program among adolescents who are OW/OB and their parent. Further treatment development and randomized controlled studies are needed.

Altered interoceptive awareness (IA) has been implicated in the pathophysiology of eating disorders; however, few comprehensive self-report measures of IA exist in eating disorders. The present study sought to validate the Multidimensional Assessment of Interoceptive Awareness (MAIA), originally developed to assess IA in individuals practicing mind-body therapies, in an eating disorder sample. Adult and adolescent patients (n = 376) completed assessments upon admission to a partial hospital programme. Analyses examined the factor structure of the MAIA, scale means, scale-scale correlations, internal consistency and construct validity. Analyses also examined associations between MAIA subscales and eating disorder symptoms. Results supported the original eight-factor structure of the MAIA. Internal consistency was acceptable, and the scales converged with associated measures. Importantly, Not Distracting, Self-regulation, Body Listening and Trusting were most strongly associated with eating disorder symptoms. Results support use of the MAIA among eating disorders and provide further support for the relevance of IA in eating disorders. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association., (Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.)

Ankylosing spondylitis (AS) is a common immune-mediated arthropathy primarily affecting the spine and pelvis. Most AS patients have subclinical intestinal inflammation, suggesting the gut microbiome and the immune response play a role in pathogenesis. Susceptibility to AS is primarily genetic, and at least 114 susceptibility variants have been identified to date. We applied bioinformatic methods utilizing epigenetic and gene and protein expression data to identify the cell types through which AS-associated variants operate. Variants were enriched in transcriptionally regulated regions in monocytes, CD4 + and CD8 + T cells, natural killer cells, regulatory T cells and B cells and mucosa from the small intestine, sigmoid colon and rectum. Weak signals were detected in bone cells, consistent with bone disease being a secondary manifestation. RNA sequencing of blood cells from AS patients and controls identified differentially expressed genes. Interrogation of expression databases showed that the upregulated genes were enriched in monocytes and downregulated genes were enriched in CD8 + T cells and natural killer cells. Gene Ontology term enrichment analysis identified microbes and the gut in the aetiology of AS. These findings identify the key immune cell types that drive the disease, and further highlight the involvement of the gut microbiome in the pathogenesis of AS.

Higher levels of care (HLC)-including inpatient hospitalization, residential treatment, partial hospitalization, and intensive outpatient treatment-are frequently utilized within routine care for eating disorders. Despite widespread use, there is limited research evaluating the efficacy of HLC, as well as clinical issues related to care in these settings. This review describes the different levels of care for eating disorders and briefly reviews the most up-to-date guidelines and research regarding how to choose a level of care. In addition, as HLC approaches for ED continue to be developed and refined, pragmatic and conceptual challenges have emerged that provide barriers to clinical efficacy and the execution of high-quality treatment research. This review includes a discussion of various issues specific to HLC, as well as a summary of recent literature addressing them.

We previously reported exome sequencing in a short-rib thoracic dystrophy (SRTD) cohort, in whom recessive mutations were identified in SRTD-associated genes in 10 of 11 cases. A heterozygous stop mutation in the known SRTD gene WDR60 was identified in the remaining case; no novel candidate gene/s were suggested by homozygous/compound heterozygous analysis. This case was thus considered unsolved. Re-analysis following an analysis pipeline update identified a homozygous mutation in C21orf2 (c.218G > C; p.Arg73Pro). This homozygous variant was previously removed at the quality control stage by the default GATK parameter "in-breeding co-efficient." C21orf2 was recently associated with both Jeune asphyxiating thoracic dystrophy (JATD) and axial spondylometaphyseal dysplasia (axial SMD); this particular mutation was reported in homozygous and compound heterozygous state in both conditions. Our case has phenotypic features of both JATD and axial SMD; and the extent of thoracic involvement appears more severe than in other C21orf2-positive cases. Identification of a homozygous C21orf2 mutation in this case emphasizes the value of exome sequencing for simultaneously screening known genes and identifying novel genes. Additionally, it highlights the importance of re-interrogating data both as novel gene associations are identified and as analysis pipelines are refined. Finally, the severity of thoracic restriction in this case adds to the phenotypic spectrum attributable to C21orf2 mutations., (© 2017 Wiley Periodicals, Inc.)

There is ample evidence that crossing over is suppressed in heterochromatin associated with centromeres and nucleolus organizers (NORs). This characteristic has been attributed to all heterochromatin, but the generalization may not be justified. To investigate the relationship of crossing over to heterochromatin that is not associated with centromeres or NORs, we used a combination of fluorescence in situ hybridization of the maize 180-bp knob repeat to show the locations of knob heterochromatin and fluorescent immunolocalization of MLH1 protein and AFD1 protein to show the locations of MLH1 foci on maize synaptonemal complexes (SCs, pachytene chromosomes). MLH1 foci correspond to the location of recombination nodules (RNs) that mark sites of crossing over. We found that MLH1 foci occur at similar frequencies per unit length of SC in interstitial knobs and in the 1 µm segments of SC in euchromatin immediately to either side of interstitial knobs. These results indicate not only that crossing over occurs within knob heterochromatin, but also that crossing over is not suppressed in the context of SC length in maize knobs. However, because there is more DNA per unit length of SC in knobs compared to euchromatin, crossing over is suppressed (but not eliminated) in knobs in the context of DNA length compared to adjacent euchromatin., (Copyright © 2017 by the Genetics Society of America.)

Immunolocalization using either fluorescence for light microscopy (LM) or gold particles for electron microscopy (EM) has become a common tool to pinpoint proteins involved in recombination during meiotic prophase. Each method has its advantages and disadvantages. For example, LM immunofluorescence is comparatively easier and higher throughput compared to immunogold EM localization. In addition, immunofluorescence has the advantages that a faint signal can often be enhanced by longer exposure times and colocalization using two (or more) probes with different absorbance and emission spectra is straightforward. However, immunofluorescence is not useful if the object of interest does not label with an antibody probe and is below the resolution of the LM. In comparison, immunogold EM localization is higher resolution than immunofluorescent LM localization, and individual nuclear structures, such as recombination nodules, can be identified by EM regardless of whether they are labeled or not. However, immunogold localization has other disadvantages including comparatively low signal-to-noise ratios, more difficult colocalization using gold particles of different sizes, and the inability to evaluate labeling efficiency before examining the sample using EM (a more expensive and time-consuming technique than LM). Here we describe a method that takes advantage of the good points of both immunofluorescent LM and EM to analyze two classes of late recombination nodules (RNs), only one of which labels with antibodies to MLH1 protein, a marker of crossovers. The method can be used readily with other antibodies to analyze early recombination nodules or other prophase I structures.

Objective: The objective of this study was to review the current eating disorders outcome literature after residential or partial hospitalization programme (PHP) treatment., Method: Articles were identified through a systematic search of PubMed and PsycINFO., Results: Twenty-two PHP and six residential treatment studies reported response at discharge and tended to find improvement. Fewer studies (nine PHP and three residential) reported outcome at some interval after discharge from treatment. These tended to find sustained improvement. A substantial proportion of patients were lost to follow-up, particularly for residential treatment. Only two follow-up studies used controlled trials; both showed efficacy for PHP compared with inpatient treatment with regard to maintaining symptom remission., Conclusions: Improvement at discharge may not predict long-term outcome. Long-term follow-up studies were confounded by high dropout rates. While higher levels of care may be essential for reversing malnutrition, there remains a lack of controlled trials showing long-term efficacy, particularly for residential treatment settings. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association., (Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association.)