Discovery of Novel, Orally Bioavailable Pyrimidine Ether-Based Inhibitors of ELOVL1.

In our efforts to identify novel small molecule inhibitors for the treatment of adrenoleukodystrophy (ALD), we conducted a high-throughput radiometric screen for inhibitors of elongation of very long chain fatty acid 1 (ELOVL1) enzyme. We developed a series of highly potent, central nervous system (CNS)-penetrant pyrimidine ether-based compounds with favorable pharmacokinetics culminating in compound 22. Compound 22 is a selective inhibitor of ELOVL1, reducing C26:0 VLCFA synthesis in ALD patient fibroblasts and lymphocytes in vitro. Compound 22 reduced C26:0 lysophosphatidyl choline (LPC), a subtype of VLCFA, in the blood of ATP binding cassette transporter D1 (ABCD1) KO mice, a murine model of ALD to near wild-type levels. Compound 22 is a low-molecular-weight, potent ELOVL1 inhibitor that may serve as a useful tool for exploring therapeutic approaches to the treatment of ALD.

Primary Ovarian Insufficiency in the Prepubertal Adolescent: A Case Report.

Although there are many etiologies for delayed puberty in adolescent-aged girls, the pediatric provider should consider primary ovarian insufficiency if estradiol remains undetectable despite elevated levels of gonadotropins. Adolescent girls with this diagnosis will need holistic care from their primary care provider, focusing on both their medical and psychosocial needs. The following case study describes a 14-year-old girl who was referred to pediatric endocrinology for delayed puberty, in the setting of increased gonadotropins and undetectable estradiol. The differential diagnosis, evaluation, and management of primary ovarian insufficiency are reviewed as well as potential long-term health considerations.

Challenges in the Treatment of Iron Deficiency Anemia in a Child With Autism Spectrum Disorder: A Case Study.

Children with autism spectrum disorder (ASD) face many challenges, including feeding problems due to behavioral issues and food aversions. Therefore, pediatric nurse practitioners need to assess for different mineral deficiencies, including iron deficiency anemia (IDA). The following case study describes a 4-year-old with ASD with persistent IDA despite typical recommendation of oral iron supplementation. Other potential etiologies of IDA are reviewed. Finally, different management approaches for managing IDA in children with ASD are described.

Systematic review and meta-analyses of foodservice interventions and their effect on nutritional outcomes and satisfaction of adult oncology patients.

AIM: An understanding of effective foodservice interventions on nutrition outcomes in adult patients with cancer is required to support clinical decision making. This systematic review aimed to determine the effect of foodservice interventions across a range of nutritional outcomes and satisfaction of hospitalised and ambulatory adult oncology patients. METHODS: The review protocol was registered with PROSPERO (CRD42016045772). Six databases were searched using search terms associated with the intervention and population. No date or language restrictions were applied. Authors applied the inclusion criteria to titles and abstracts and then full-text papers. The final library was assessed for risk of bias. Outcome data were combined narratively and, where possible, by meta-analysis. RESULTS: From the title and abstract review of 4414 studies, 12 studies testing the effect of foodservice interventions were included in this review. Meta-analyses demonstrated significantly greater energy (mean difference 1.54 MJ/day; 95% CI 0.85-2.23 MJ/day) and protein (mean difference 18.98 g/day; 95% CI 11.58-26.39 g/day) intake through the addition of oral nutrition supplements. Other positive effects on anthropometric outcomes were also recorded. Patient satisfaction was enhanced through other foodservice interventions. CONCLUSIONS: Limited original research was found exploring the effect of foodservice interventions in oncology patients. Significant findings were found in favour of the intervention across a range of nutritional outcomes, suggesting that foodservice interventions may improve clinical outcomes and satisfaction in this population. Effective foodservice interventions for oncology patients remain under-researched, so we encourage dietitians and foodservice staff to implement rigorous study designs to evaluate and publish interventions in this clinical group.

UTILITY OF PSYCHOLOGICAL SCREENING OF YOUNG ADULTS WITH TYPE 1 DIABETES TRANSITIONING TO ADULT PROVIDERS.

OBJECTIVE: Screening for depression, diabetes distress, and disordered eating in youth with type 1 diabetes (T1D) is recommended, as these comorbidities contribute to poor glycemic control. No consensus exists on which measures are optimal, and most previous studies have used nondisease-specific measures. We examined the utility of screening for these disorders using two disease-specific and one general measure at the time of transition from pediatric to adult care. METHODS: Forty-three young adults from a T1D transition clinic completed the Patient Health Questionnaire, the Diabetes Distress Scale, and the Diabetes Eating Problem Survey-Revised. Chart review determined if clinicians noted similar symptoms during the year prior to transition. Metabolic data were also recorded. RESULTS: Chart review identified 5 patients with depressive symptoms and 8 patients with diabetes distress. Screening identified 2 additional patients with depressive symptoms and 1 additional patient with diabetes distress. Of those noted to have symptomatic depression or diabetes distress on chart review, several subsequently screened negative on transition. Disordered eating was not detected by chart review, but 23.5% screened positive on transition. While depression, diabetes distress, and disordered eating positively correlated with glycated hemoglobin (HbA1c) (r = 0.31, P = .05; r = 0.40, P = .009; r = 0.63, P<.001, respectively), disordered eating accounted for the majority of observed variance (df = 1; F = 18.6; P<.001). Even though HbA1c was higher in patients with versus without disordered eating (P<.001), body mass index did not differ between the 2 groups (P = .51). CONCLUSION: In young adults with T1D, formal screening provides an opportunity to detect psychological problems, which, when treated, may help optimize metabolic control during the transition process. ABBREVIATIONS: T1D = type 1 diabetes HbA1C = hemoglobin A1c YCDP = Yale Children's Diabetes Program PHQ-8 = Patient Health Questionnaire-8 DDS = Diabetes Distress Scale DEPS-R = Diabetes Eating Problem Survey-Revised.

A critical exploration of the International Classification of Functioning, Disability, and Health (ICF) framework from the perspective of oncology: recommendations for revision.

BACKGROUND: In 2001, the World Health Organization developed the International Classification of Functioning, Disability, and Health (ICF) framework in an effort to attend to the multidimensional health-related concerns of individuals. Historically, although the ICF has frequently been used in a rehabilitation-based context, the World Health Organization has positioned it as a universal framework of health and its related states. Consequently, the ICF has been utilized for a diverse array of purposes in the field of oncology, including: evaluating functioning in individuals with cancer, guiding assessment in oncology rehabilitation, assessing the comprehensiveness of outcome measures utilized in oncology research, assisting in health-related quality of life instrument selection, and comparing the primary concerns of health professionals with those of their patients. DISCUSSION: Examination of the ICF through the lens of cancer care highlights the fact that this framework can be a valuable tool to facilitate comprehensive care in oncology, but it currently possesses some areas of limitation that require conceptual revision; to this end, several recommendations have been proposed. Specifically, these proposed recommendations center on the following three areas of the ICF framework: (1) the replacement of the term "health condition" with the more inclusive and dynamic term "health state;" (2) the continuing development and refinement of the personal factors component to ensure issues such as comorbidities can be accounted for appropriately; and (3) the inclusion of a mechanism to account for the subjective dimension of health and functioning (eg, quality of life). SUMMARY: It is through the expansion of these conceptual parameters that the ICF may become more relevant and applicable to the field of oncology. With these important revisions, the ICF has the potential to provide a broader biopsychosocial perspective of care that captures the diverse range of concerns that arise throughout the continuum of care in oncology.