Programmable RNA sensing for cell monitoring and manipulation.

RNA is a central and universal mediator of genetic information underlying the diversity of cell types and cell states, which together shape tissue organization and organismal function across species and lifespans. Despite numerous advances in RNA sequencing technologies and the massive accumulation of transcriptome datasets across the life sciences1,2, the dearth of technologies that use RNAs to observe and manipulate cell types remains a bottleneck in biology and medicine. Here we describe CellREADR (Cell access through RNA sensing by Endogenous ADAR), a programmable RNA-sensing technology that leverages RNA editing mediated by ADAR to couple the detection of cell-defining RNAs with the translation of effector proteins. Viral delivery of CellREADR conferred specific cell-type access in mouse and rat brains and in ex vivo human brain tissues. Furthermore, CellREADR enabled the recording and control of specific types of neurons in behaving mice. CellREADR thus highlights the potential for RNA-based monitoring and editing of animal cells in ways that are specific, versatile, simple and generalizable across organ systems and species, with wide applications in biology, biotechnology and programmable RNA medicine.

Long-term cardiovascular consequences of adolescent anorexia nervosa.

BACKGROUND: Anorexia nervosa (AN) is associated with maladaptive cardiovascular changes. This study investigated whether individuals who recovered from AN during adolescence experience long-term cardiovascular risk in early adulthood. METHODS: Former AN patients discharged from the Royal Children's and Monash Children's Hospital Eating Disorder Services in Melbourne, Australia underwent cardiovascular testing. Measurements were performed using an oscillometric device for blood pressure and pulse wave velocity, ultrasound for carotid wall structure/function, resting electrocardiogram for heart-rate variability, and the EndoPat 2000 (Itamar) system for endothelial function. Patient measures were compared to healthy controls and/or normal thresholds. RESULTS: Ninety-one percent of the former AN patients (N = 22) and controls (N = 66) were female, aged approximately 25 years, with a healthy body mass index. The mean time interval from AN recovery to participation was 7.4 years. Pulse wave velocity was lower in the former AN patients than controls. Carotid intima-media thickness was not different; however, carotid distensibility and compliance were lower, and the elastic modulus higher in the former AN patients. Greater vagal tone was observed and endothelial dysfunction was evident in 46% of the former patients. CONCLUSIONS: Young adults who recovered from adolescent AN exhibit persistent cardiovascular adaptations. Routine cardiovascular monitoring could manage potential disease risk. IMPACT: Cardiovascular complications are common in patients with anorexia nervosa (AN) and population studies have revealed that developmental adaptations in response to undernutrition have long-term consequences for cardiovascular health. In this study of young adults treated for AN during adolescence, there was evidence of increased carotid artery stiffness, reduced aortic stiffness, vagal hyperactivity, and endothelial dysfunction in early adulthood when compared to healthy controls. It is important to consider the cardiovascular health of patients with AN beyond achieving medical stability. Interventions that monitor cardiovascular health could minimise the burden of future cardiovascular disease.

Epithelia-Sensory Neuron Cross Talk Underlies Cholestatic Itch Induced by Lysophosphatidylcholine.

BACKGROUND & AIMS: Limited understanding of pruritus mechanisms in cholestatic liver diseases hinders development of antipruritic treatments. Previous studies implicated lysophosphatidic acid (LPA) as a potential mediator of cholestatic pruritus. METHODS: Pruritogenicity of lysophosphatidylcholine (LPC), LPA's precursor, was examined in naïve mice, cholestatic mice, and nonhuman primates. LPC's pruritogenicity involving keratinocyte TRPV4 was studied using genetic and pharmacologic approaches, cultured keratinocytes, ion channel physiology, and structural computational modeling. Activation of pruriceptor sensory neurons by microRNA-146a (miR-146a), secreted from keratinocytes, was identified by in vitro and ex vivo Ca2+ imaging assays. Sera from patients with primary biliary cholangitis were used for measuring the levels of LPC and miR-146a. RESULTS: LPC was robustly pruritic in mice. TRPV4 in skin keratinocytes was essential for LPC-induced itch and itch in mice with cholestasis. Three-dimensional structural modeling, site-directed mutagenesis, and channel function analysis suggested a TRPV4 C-terminal motif for LPC binding and channel activation. In keratinocytes, TRPV4 activation by LPC induced extracellular release of miR-146a, which activated TRPV1+ sensory neurons to cause itch. LPC and miR-146a levels were both elevated in sera of patients with primary biliary cholangitis with itch and correlated with itch intensity. Moreover, LPC and miR-146a were also increased in sera of cholestatic mice and elicited itch in nonhuman primates. CONCLUSIONS: We identified LPC as a novel cholestatic pruritogen that induces itch through epithelia-sensory neuron cross talk, whereby it directly activates skin keratinocyte TRPV4, which rapidly releases miR-146a to activate skin-innervating TRPV1+ pruriceptor sensory neurons. Our findings support the new concept of the skin, as a sensory organ, playing a critical role in cholestatic itch, beyond liver, peripheral sensory neurons, and central neural pathways supporting pruriception.

Impact of the coronavirus pandemic on anorexia nervosa and atypical anorexia nervosa presentations to an Australian tertiary paediatric hospital.

AIM: The coronavirus (COVID-19) pandemic has led to increased concerns about adolescent mental health. This study aimed to determine the effect of the pandemic on adolescent eating disorders (EDs) by measuring changes in the number and severity of presentations to an Australian paediatric ED service that utilises a standardised approach to triage and assessment. METHODS: A 4-year retrospective chart review (2017-2020) of all patients (n = 457) presenting to the Royal Children's Hospital Eating Disorder Service, Melbourne, was undertaken. The incidence of each diagnosis and measures of condition severity were extracted from the database and patient medical records. Clinical comments relating to the impact of COVID-19, on both ED behaviours and treatment, were also noted. RESULTS: Annual presentations increased from a mean of 98.7 per annum from 2017 to 2019 to 161 in 2020 (63% increase). COVID-19 restrictions were reported to be a trigger for ED behaviours in 40.4% of adolescents diagnosed with anorexia nervosa in 2020. There was no significant difference in severity across years despite increased cases. CONCLUSIONS: The dramatic increase in presentations has implications for primary health and paediatric care as well as specialist ED services. Increased support is needed for EDs during this time.

Family-based treatment for adolescents with anorexia nervosa: A long-term psychological follow-up.

AIM: Family-based treatment (FBT) has the greatest evidence base for the treatment of adolescents with anorexia nervosa (AN). However, little is known about the long-term outcomes for patients who receive FBT. The current study aimed to investigate the long-term psychological health of former patients who received FBT for AN during adolescence. METHODS: Former patients diagnosed and treated for AN at the Royal Children's Hospital and Monash Children's Hospital (N = 36) in Melbourne, Australia completed self-report questionnaires to assess eating, exercising, mood and the impact of the coronavirus (COVID-19) pandemic. Patient scores were compared to healthy controls (N = 29) and normative data. RESULTS: The eating and exercising behaviours of the patients who formerly had AN were comparable to controls. However, the former patients experience significantly greater levels of depression, anxiety, and stress than the controls (P < 0.05). The COVID-19 pandemic appeared to impact the former patients and controls to a similar extent across quantifiable criteria. CONCLUSIONS: This study extends previous research highlighting FBT as an effective intervention for adolescents with AN. Positive short- and long-term patient outcomes can be achieved with this form of treatment.

Gender-based clinical differences in evidence-based treatment for adolescent anorexia nervosa: analysis of aggregated randomized controlled trials.

PURPOSE: Boys represent a small proportion of samples in randomized clinical trials (RCT) investigating evidence-based treatment for adolescents with anorexia nervosa (AN). Consequently, knowledge of potential gender differences in clinical characteristics and treatment response in adolescents is considerably limited. METHODS: Secondary analyses of aggregated data from two RCTs were used to characterize baseline and end-of-treatment clinical features in male and female adolescents with AN (n = 228, 10.53% male). Mixed analyses of variance were used to investigate potential gender differences in treatment response relative to weight outcomes (% median BMI) and eating disorder cognitions (Eating Disorder Examination Global scores; EDE). RESULTS: There were no significant gender differences in prior inpatient care, illness duration, psychiatric comorbidity, or psychotropic medication use at baseline. Nor were there significant gender differences in binge eating, purging, or driven exercise at baseline or end-of-treatment. Girls reported elevated weight and shape concern compared to boys at baseline but overall reduction in EDE Global scores over the course of treatment did not differ according to gender. Boys gained more relative weight during treatment than girls, but this difference was statistically non-significant. CONCLUSION: Overall findings do not suggest significant differences in treatment outcome relative to weight or ED cognitions, by gender. Current evidence suggests that, with the exception of shape and weight concerns, boys present with cognitive and behavioral symptoms as severe as their female counterparts which underscores the need for increased accuracy in assessment of these disorders in boys and young men. LEVEL OF EVIDENCE: Level 1, secondary data analysis of randomized controlled trials.

Family-based treatment for adolescent anorexia nervosa: Outcomes of a stepped-care model.

OBJECTIVE: Stepped-care models of treatment are underexplored in eating disorders. To enhance treatment outcomes, and informed by literature about adaptations to family-based treatment (FBT), we developed an FBT-based stepped-care model for adolescents with anorexia nervosa (AN) that was consistent with family preference (i.e., tailored) and responsive to adolescent needs (i.e., intensity). The aim of this study was to evaluate the effectiveness of this model in terms of remission at end-of-treatment. METHOD: Adolescents (N = 82), aged 12-18 years (M = 15.1, SD = 1.8) and meeting Diagnostic and Statistical Manual of Mental Disorders 5th Edition criteria for AN, were assessed at baseline, Weeks 24 and 48. FBT was tailored to family preference and clinical need, with 16-18 sessions by Week 24. This was followed by three FBT booster sessions or an extension of FBT plus booster sessions (Week 48). The primary outcome was defined as weight > 95% of %median body mass index plus within 1 SD of the Eating Disorder Examination (EDE) global score community norms. RESULTS: Remission rates were 45.1% and 52.4% at Weeks 24 and 48, respectively. Commensurable improvements were evident across secondary outcomes (e.g., EDE subscale scores). As a reference point, remission rates compared positively with results from a recent randomized clinical trial from the same center and at the same time points (Week 24:45.1% vs. 32.1% and Week 48:52.4% vs. 30.2%). Controlling for propensity score, no statistically significant differences were observed. DISCUSSION: This stepped-care model, designed to be responsive to the individual needs of adolescents and their families, achieved encouraging rates of remission. This study provides an important signal that supports future clinical trials of stepped-care models for adolescents with AN.

Bisphenol A delays the perinatal chloride shift in cortical neurons by epigenetic effects on the Kcc2 promoter.

Bisphenol A (BPA) is a ubiquitous compound that is emerging as a possible toxicant during embryonic development. BPA has been shown to epigenetically affect the developing nervous system, but the molecular mechanisms are not clear. Here we demonstrate that BPA exposure in culture led to delay in the perinatal chloride shift caused by significant decrease in potassium chloride cotransporter 2 (Kcc2) mRNA expression in developing rat, mouse, and human cortical neurons. Neuronal chloride increased correspondingly. Treatment with epigenetic compounds decitabine and trichostatin A rescued the BPA effects as did knockdown of histone deacetylase 1 and combined knockdown histone deacetylase 1 and 2. Furthermore, BPA evoked increase in tangential interneuron migration and increased chloride in migrating neurons. Interestingly, BPA exerted its effect in a sexually dimorphic manner, with a more accentuated effect in females than males. By chromatin immunoprecipitation, we found a significant increase in binding of methyl-CpG binding protein 2 to the "cytosine-phosphate-guanine shores" of the Kcc2 promoter, and decrease in binding of acetylated histone H3K9 surrounding the transcriptional start site. Methyl-CpG binding protein 2-expressing neurons were more abundant resulting from BPA exposure. The sexually dimorphic effect of BPA on Kcc2 expression was also demonstrated in cortical neurons cultured from the offspring of BPA-fed mouse dams. In these neurons and in cortical slices, decitabine was found to rescue the effect of BPA on Kcc2 expression. Overall, our results indicate that BPA can disrupt Kcc2 gene expression through epigenetic mechanisms. Beyond increase in basic understanding, our findings have relevance for identifying unique neurodevelopmental toxicity mechanisms of BPA, which could possibly play a role in pathogenesis of human neurodevelopmental disorders.

Parent-focused treatment for adolescent anorexia nervosa: a study protocol of a randomised controlled trial.

BACKGROUND: Family-based treatment is an efficacious outpatient intervention for medically stable adolescents with anorexia nervosa. Previous research suggests family-based treatment may be more effective for some families when parents and adolescents attend separate therapy sessions compared to conjoint sessions. Our service developed a novel separated model of family-based treatment, parent-focused treatment, and is undertaking a randomised controlled trial to compare parent-focused treatment to conjoint family-based treatment. METHODS/DESIGN: This randomised controlled trial will recruit 100 adolescents aged 12-18 years with DSM-IV anorexia nervosa or eating disorder not otherwise specified (anorexia nervosa type). The trial commenced in 2010 and is expected to be completed in 2015. Participants are recruited from the Royal Children's Hospital Eating Disorders Program, Melbourne, Australia. Following a multidisciplinary intake assessment, eligible families who provide written informed consent are randomly allocated to either parent-focused treatment or conjoint family-based treatment. In parent-focused treatment, the adolescent sees a clinical nurse consultant and the parents see a trained mental health clinician. In conjoint family-based treatment, the whole family attends sessions with the mental health clinician. Both groups receive 18 treatment sessions over 6 months and regular medical monitoring by a paediatrician. The primary outcome is remission at end of treatment and 6 and 12 month follow up, with remission defined as being ≥ 95% expected body weight and having an eating disorder symptom score within one standard deviation of community norms. The secondary outcomes include partial remission and changes in eating pathology, depressive symptoms and self-esteem. Moderating and mediating factors will also be explored. DISCUSSION: This will be first randomised controlled trial of a parent-focused model of family-based treatment of adolescent anorexia nervosa. If found to be efficacious, parent-focused treatment will offer an alternative approach for clinicians who treat adolescents with anorexia nervosa. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ACTRN12610000216011.

Carotid wave analysis in young adults with a history of adolescent anorexia nervosa: a case control study.

BACKGROUND: Anorexia nervosa (AN) is associated with abnormalities that may increase the risk of future cardiovascular disease. This study assessed the cardiovascular health of individuals who recovered from AN during adolescence by conducting wave power analysis. METHODS: Former AN patients discharged from the Royal Children's and Monash Children's Hospitals (N = 17) in Melbourne, Australia underwent ultrasound imaging of the right carotid artery. Wave power analysis was conducted to assess biomechanical interactions of the cardiovascular system. Patient measures were compared to healthy controls (N = 51). RESULTS: Eighty-eight percent of the former AN patients and controls were female, aged approximately 25 years, with a healthy body mass index. Mean carotid flow and pulsatility index were not different between groups. Carotid arterial strain and distensibility were lower, and the wave speed and beta stiffness index higher in the former AN patients. Characteristic impedance was not different nor were the forward and backward wave amplitudes. However, wave reflection indices (ratios of backward-to-forward compression wave area, and wave-related effect on pressure and hydraulic power) were 12-18% lower in the former AN patients (p < 0.05). CONCLUSIONS: Increased carotid artery stiffness and reduced wave reflection are evident in young adults who recovered from adolescent AN. This may relate to an adaptive process that helps to maintain or restore flow and characteristic impedance despite increased vessel stiffness, with this warranting future investigation.

Anorexia nervosa (AN) is an eating disorder which may cause permanent changes in the heart and blood vessels. Blood flow properties can provide information on the health of a patient's heart and blood vessels. In this study of young adults who recovered from adolescent AN, blood flow analysis revealed altered properties compared to controls who had never experienced an eating disorder. These alterations may help to maintain or restore blood flow despite unhealthy changes in the blood vessels themselves. Further investigation is needed to better understand how the heart and blood vessels change during and after AN to guide treatments and ongoing care. Regular assessment of the heart and blood vessels after AN recovery could identify and monitor possible health risks early.

Highly conductive carbon nanotube matrix accelerates developmental chloride extrusion in central nervous system neurons by increased expression of chloride transporter KCC2.

Exceptional mechanical and electrical properties of carbon nanotubes (CNT) have attracted neuroscientists and neural tissue engineers aiming to develop novel devices that interface with nervous tissues. In the central nervous system (CNS), the perinatal chloride shift represents a dynamic change that forms the basis for physiological actions of γ-aminobutyric acid (GABA) as an inhibitory neurotransmitter, a process of fundamental relevance for normal functioning of the CNS. Low intra-neuronal chloride concentrations are maintained by a chloride-extruding transporter, potassium chloride cotransporter 2 (KCC2). KCC2's increasing developmental expression underlies the chloride shift. In neural injury, repressed KCC2 expression plays a co-contributory role by corrupting inhibitory neurotransmission. Mechanisms of Kcc2 up-regulation are thus pertinent because of their medical relevance, yet they remain elusive. Here, it is shown that primary CNS neurons originating from the cerebral cortex, cultured on highly-conductive few-walled-CNT (fwCNT) have a strikingly accelerated chloride shift caused by increased KCC2 expression. KCC2 upregulation is dependent on neuronal voltage-gated calcium channels (VGCC) and, furthermore, on calcium/calmodulin-dependent kinase II, which is linked to VGCC-mediated calcium-influx. It is also demonstrated that accelerated Kcc2 transcription in brain-slices prepared from genetically-engineered reporter mice, in which Kcc2 promoter drives luciferase, when the cerebral cortex of these mice is exposed to fwCNT-coated devices. Based on these findings, whether fwCNT can enhance neural engineering devices for the benefit of neural injury conditions associated with elevated neuronal intracellular chloride concentration-such as pain, epilepsy, traumatic neural injury and ischemia-can now be addressed. Taken together, our novel insights illustrate how fwCNTs can promote low neuronal chloride in individual neurons and thus inhibitory transmission in neural circuits.

Working with young people: evaluation of an education resource for medical trainees.

AIM: Many health professionals report interest in consulting more effectively with young people but have unmet training needs. We set out to evaluate a teaching resource in adolescent health and medicine that was designed for Australian trainees in specialist medicine. METHODS: Thirty-two paediatric and adult trainees of the Royal Australasian College of Physicians completed a pre-evaluation questionnaire to assess attitudes and confidence in working with young people. They were then provided with a training resource and, 6 weeks later, completed a post-evaluation questionnaire. Repeated-measures anovas were used to assess changes in attitudes, self-reported knowledge and confidence by trainee type. χ(2) -tests were used to compare variation in the use of and opinions about the resource. RESULTS: Trainees' awareness of the health issues that affect young people, confidence in working with young people and confidence in their knowledge greatly improved after using the resource. Beforehand, adult medicine trainees scored lower than paediatric trainees. A relatively higher rate of improvement resulted in similar scores between trainee types after using the resource, which was rated equally highly by the different groups of trainees. CONCLUSIONS: As a result of significant gains in the confidence of specialist medicine trainees after access to the resource, it will now be made available for Australian trainees in specialist medicine.

Spinal cord dorsal horn sensory gate in preclinical models of chemotherapy-induced painful neuropathy and contact dermatitis chronic itch becomes less leaky with Kcc2 gene expression-enhancing treatments.

Low intraneuronal chloride in spinal cord dorsal horn (SCDH) pain relay neurons is of critical relevance for physiological transmission of primary sensory afferents because low intraneuronal chloride dictates GABA-ergic and glycin-ergic neurotransmission to be inhibitory. If neuronal chloride rises to unphysiological levels, the primary sensory gate in the spinal cord dorsal horn becomes corrupted, with resulting behavioral hallmarks of hypersensitivity and allodynia, for example in pathological pain. Low chloride in spinal cord dorsal horn neurons relies on the robust gene expression of Kcc2 and sustained transporter function of the KCC2 chloride-extruding electroneutral transporter. Based on a recent report where we characterized the GSK3-inhibitory small molecule, kenpaullone, as a Kcc2 gene expression-enhancer that potently repaired diminished Kcc2 expression and KCC2 transporter function in SCDH pain relay neurons, we extend our recent findings by reporting (i) effective pain control in a preclinical model of taxol-induced painful peripheral neuropathy that was accomplished by topical application of a TRPV4/TRPA1 dual-inhibitory compound (compound 16-8), and was associated with the repair of diminished Kcc2 gene expression in the SCDH; and (ii) potent functioning of kenpaullone as an antipruritic in a DNFB contact dermatitis preclinical model. These observations suggest that effective peripheral treatment of chemotherapy-induced painful peripheral neuropathy impacts the pain-transmitting neural circuit in the SCDH in a beneficial manner by enhancing Kcc2 gene expression, and that chronic pruritus might be relayed in the primary sensory gate of the spinal cord, following similar principles as pathological pain, specifically relating to the critical functioning of Kcc2 gene expression and the KCC2 transporter function.

Eating disorders - early identification in general practice.

BACKGROUND: Eating disorders are complex illnesses that impact on both the physical and socio-emotional health of young people, and contribute to significant morbidity. Dieting behaviours and body image concerns are common in adolescence and it can be challenging to identify those at the extreme end of this spectrum who are at risk of an eating disorder. OBJECTIVE: This article presents a brief overview of eating disorders, with a focus on early identification in general practice. An approach to diagnosis is outlined together with an update on evidence based treatments. DISCUSSION: General practitioners are uniquely placed to recognise early onset eating disorders, offer intervention and help coordinate and monitor treatment. Early detection and management may contribute to better outcomes.

Repurposing cancer drugs identifies kenpaullone which ameliorates pathologic pain in preclinical models via normalization of inhibitory neurotransmission.

Inhibitory GABA-ergic neurotransmission is fundamental for the adult vertebrate central nervous system and requires low chloride concentration in neurons, maintained by KCC2, a neuroprotective ion transporter that extrudes intracellular neuronal chloride. To identify Kcc2 gene expression­enhancing compounds, we screened 1057 cell growth-regulating compounds in cultured primary cortical neurons. We identified kenpaullone (KP), which enhanced Kcc2/KCC2 expression and function in cultured rodent and human neurons by inhibiting GSK3ß. KP effectively reduced pathologic pain-like behavior in mouse models of nerve injury and bone cancer. In a nerve-injury pain model, KP restored Kcc2 expression and GABA-evoked chloride reversal potential in the spinal cord dorsal horn. Delta-catenin, a phosphorylation-target of GSK3ß in neurons, activated the Kcc2 promoter via KAISO transcription factor. Transient spinal over-expression of delta-catenin mimicked KP analgesia. Our findings of a newly repurposed compound and a novel, genetically-encoded mechanism that each enhance Kcc2 gene expression enable us to re-normalize disrupted inhibitory neurotransmission through genetic re-programming.

Novel repression of Kcc2 transcription by REST-RE-1 controls developmental switch in neuronal chloride.

Transcriptional upregulation of Kcc2b, the gene variant encoding the major isoform of the KCC2 chloride transporter, underlies a rapid perinatal decrease in intraneuronal chloride concentration (chloride shift), which is necessary for GABA to act inhibitory. Here we identify a novel repressor element-1 (RE-1) site in the 5' regulatory region of Kcc2b. In primary cortical neurons, which recapitulate the chloride shift in culture, the novel upstream RE-1 together with a known intronic RE-1 site function in concerted interaction to suppress Kcc2b transcription. With critical relevance for the chloride shift, only in the presence of the dual RE-1 site could inhibition of REST upregulate Kcc2b transcription. For this, we confirmed increased KCC2 protein expression and decreased intraneuronal chloride. Kcc2b developmental upregulation was potentiated by BDNF application, which was fully dependent on the presence of dual RE-1. In addition, the developmental chloride shift and GABA switch, from excitatory to inhibitory action, was accelerated by REST inhibition and slowed by REST overexpression. These results identify the REST-dual RE-1 interaction as a novel mechanism of transcriptional Kcc2b upregulation that significantly contributes to the ontogenetic shift in chloride concentration and GABA action in cortical neurons, which is fundamental for brain function in health and disease. Thus, we present here a new logic for the perinatal chloride shift, which is critical for establishment of GABAergic cortical inhibitory neurotransmission.

Adolescent and Parent Experience of Care at a Family-Based Treatment Service for Eating Disorders.

OBJECTIVE: Incorporating consumer perspectives is an important but often overlooked opportunity to optimize treatment engagement and outcomes for adolescents with eating disorders. This study explored the experience of care of adolescents and their parents at a multidisciplinary specialist eating disorders service providing family-based treatment (FBT) as first-line treatment. METHOD: Eighty-five adolescents and 145 parents who completed FBT at the service between 2013 and 2015 were surveyed in 2017 about their experience of care. A study-designed survey asked respondents to rate on Likert scales their experience of service access, intake assessment, education, support, interactions with the treatment team, recovery, and the discharge process. Open-ended comments on helpful and unhelpful aspects of the service provided further context on the ratings. RESULTS: Overall families were very positive about their experience, particularly in regard to assessment, education, interactions with the team, and achieving physical health. Although parents tended to be more satisfied, adolescents also held the service in high regard. Some areas were identified that could be improved, including treatment delays, carer support, therapeutic alliance, and preparation for discharge. CONCLUSIONS: Surveying families about their experience of care provides an important opportunity to identify service strengths as well as services gaps. The results indicated several areas that specialist eating disorder services could focus on to ensure that the services provided, including FBT, fully meet the needs of families and optimize adolescents' treatment experiences.

Delivery of Family-Based Treatment for Adolescent Anorexia Nervosa in a Public Health Care Setting: Research Versus Non-Research Specialty Care.

Comparing evidence-based psychotherapy (EBP) to usual care typically demonstrates the superiority of EBPs, although this has not been studied for eating disorders EBPs such as family-based treatment (FBT). The current study set out to examine weight outcomes for adolescents with anorexia nervosa who received FBT through a randomized clinical research trial (RCT, n = 54) or non-research specialty care (n = 56) at the same specialist pediatric eating disorder service. Weight was recorded throughout outpatient treatment (up to 18 sessions over 6 months), as well as at 6- and 12-month follow-up. Survival curves were used to examine time to weight restoration [greater than 95% median body mass index (mBMI)] as predicted by type of care (RCT vs. non-research specialty care), baseline clinical and demographic characteristics, and their potential interaction. Results did not indicate a significant main effect for type of care, but there was a significant effect for baseline weight (p = .03), such that weight restoration was achieved faster across both treatment types for those with a higher initial %mBMI. These data suggest that weight restoration achieved in non-research specialty care FBT was largely similar to that achieved in a controlled research trial. CLINICAL TRIAL REGISTRATION: http://www.anzctr.org.au/, identifier ACTRN12610000216011.

Adolescents with a chronic condition: challenges living, challenges treating.

In this review, we aim to focus attention on the interaction between adolescents with chronic conditions and the health systems that support them. At least 12% of adolescents live with a chronic condition. Some conditions are characterised by increasing incidence (eg, diabetes) or improving survival rates (eg, cystic fibrosis), while others are concerning because of differentially poorer outcomes in adolescents in comparison to both children and adults (eg cancer). Growing evidence suggests that young people with chronic conditions are doubly disadvantaged--engaging in risky behaviours to at least similar if not higher rates as healthy peers, while having the potential for greater adverse health outcomes from these behaviours. In addition to efforts at improving survival, in order to improve their life chances, we need to better understand how the social and emotional outcomes of young people with a chronic disease can be improved, and better support young people's emerging capacity for self-management.

Functional characterization of small CTD phosphatases.

The carboxyl-terminal domain (CTD) of the largest subunit of RNA polymerase (RNAP) II undergoes reversible phosphorylation with each round of transcription essential for the regulation of gene expression. A family of small CTD phosphatases (SCPs) was identified based on a homology search to TFIIF-associating CTD phosphatase 1 (FCP1). Unlike FCP1, SCP preferentially catalyze the dephosphorylation of Ser5 within the CTD and is especially active toward RNAP II phosphorylated by TFIIH (1). Recently, SCP1 was demonstrated as a transcriptional regulator that acts to silence neuronal genes (2). This chapter describes the procedures for various assays involved in the discovery and functional characterization of SCPs.