Protocol for the Promoting Resilience in Stress Management (PRISM) Intervention: A Multi-Site Randomized Controlled Trial for Adolescents and Young Adults with Advanced Cancer

Background Adolescents and young adults (AYAs) with cancer are at high risk of poor psychosocial outcomes, and evidence-based interventions designed to meet their psychosocial and communication needs are lacking. The main objective of this project is to test the efficacy of a new adaptation of the Promoting Resilience in Stress Management intervention for AYAs with Advanced Cancer (PRISM-AC). Methods/design The PRISM-AC trial is a 2-arm, parallel, non-blinded, multisite, randomized controlled trial. 144 participants with advanced cancer will be enrolled and randomized to either usual, non-directive, supportive care without PRISM-AC (“control” arm) or with PRISM-AC (“experimental” arm). PRISM is a manualized, skills-based training program comprised of four 30–60 min, one-on-one sessions targeting AYA-endorsed resilience resources (stress-management, goal-setting, cognitive-reframing, and meaning-making). It also includes a facilitated family meeting and a fully equipped smartphone app. The current adaptation includes an embedded advance care planning module. English- or Spanish-speaking individuals 12–24 years old with advanced cancer (defined as progressive, recurrent, or refractory disease, or any diagnosis associated with \u3c 50% survival) receiving care at 4 academic medical centers are eligible. Patients’ caregivers are also eligible to participate in this study if they are able to speak and read English or Spanish, and are cognitively and physically able to participate. Participants in all groups complete surveys querying patient-reported outcomes at the time of enrollment and 3-, 6-, 9-, and 12-months post-enrollment. The primary outcome of interest is patient-reported health-related quality of life (HRQOL) and secondary outcomes of interest include patient anxiety, depression, resilience, hope and symptom burden, parent/caregiver anxiety, depression and health-related quality of life, and family palliative care activation. We will conduct intention-to-treat analysis to compare the group means of primary and secondary outcomes between PRISM-AC arm and control arm with regression models. Discussion This study will provide methodologically rigorous data and evidence regarding a novel intervention to promote resilience and reduce distress among AYAs with advanced cancer. This research has the potential to offer a practical, skills-based curriculum designed to improve outcomes for this high-risk group. Trial registration ClinicalTrials.gov Identifier NCT03668223, September 12, 2018

Physicians’ Perspectives on the Diagnosis and Treatment of Chronic Nonbacterial Osteomyelitis

Background/Purpose. Understanding the practices of pediatric rheumatologists in diagnosing and treating chronic nonbacterial osteomyelitis (CNO) can provide important information to guide the development of consensus treatment plans. The objectives of this study were to determine physicians’ approaches to (1) diagnosing and monitoring CNO, (2) ordering a bone biopsy, and (3) making treatment decisions. Methods. A survey was distributed among members of the Childhood Arthritis and Rheumatology Research Alliance using a web-based questionnaire. Results. 121 of 277 (41%) attending physician members completed the survey. Plain radiographs (89%) were most commonly used followed by regional MRI (78%), bone scintigraphy (43%), and whole-body MRI (36%). The top three reasons for performing a biopsy were constitutional findings (66%), unifocal bone lesions (64%), and nocturnal bone pain (45%). Nearly all responders (95%) prescribed nonsteroidal anti-inflammatory drugs (NSAIDs) as initial therapy. For patients who failed NSAID treatment, methotrexate (67%), tumor necrosis factor inhibitors (65%), and bisphosphonates (46%) were the next most commonly used treatments. The presence of a spinal lesion increased the use of bisphosphonate treatment. Conclusion. The diagnostic approach and disease activity monitoring for CNO varied among surveyed physicians. Our survey findings provided important background for the development of consensus treatment plans for CNO

Cyclophilin A is an inflammatory mediator that promotes atherosclerosis in apolipoprotein E–deficient mice

Cyclophilin A promotes atherosclerosis in part by inducing reactive oxygen species and promoting endothelial cell apoptosis and macrophage recruitment into lesions

Evolution of major milk proteins in Mus musculus and Mus spretus mouse species: a genoproteomic analysis

<p>Abstract</p> <p>Background</p> <p>Due to their high level of genotypic and phenotypic variability, <it>Mus spretus </it>strains were introduced in laboratories to investigate the genetic determinism of complex phenotypes including quantitative trait loci. <it>Mus spretus </it>diverged from <it>Mus musculus </it>around 2.5 million years ago and exhibits on average a single nucleotide polymorphism (SNP) in every 100 base pairs when compared with any of the classical laboratory strains. A genoproteomic approach was used to assess polymorphism of the major milk proteins between SEG/Pas and C57BL/6J, two inbred strains of mice representative of <it>Mus spretus </it>and <it>Mus musculus </it>species, respectively.</p> <p>Results</p> <p>The milk protein concentration was dramatically reduced in the SEG/Pas strain by comparison with the C57BL/6J strain (34 ± 9 g/L <it>vs</it>. 125 ± 12 g/L, respectively). Nine major proteins were identified in both milks using RP-HPLC, bi-dimensional electrophoresis and MALDI-Tof mass spectrometry. Two caseins (β and α_s1) and the whey acidic protein (WAP), showed distinct chromatographic and electrophoresis behaviours. These differences were partly explained by the occurrence of amino acid substitutions and splicing variants revealed by cDNA sequencing. A total of 34 SNPs were identified in the coding and 3'untranslated regions of the SEG/Pas <it>Csn1s1 </it>(11), <it>Csn2 </it>(7) and <it>Wap </it>(8) genes. In addition, a 3 nucleotide deletion leading to the loss of a serine residue at position 93 was found in the SEG/Pas <it>Wap </it>gene.</p> <p>Conclusion</p> <p>SNP frequencies found in three milk protein-encoding genes between <it>Mus spretus </it>and <it>Mus musculus </it>is twice the values previously reported at the whole genome level. However, the protein structure and post-translational modifications seem not to be affected by SNPs characterized in our study. Splicing mechanisms (cryptic splice site usage, exon skipping, error-prone junction sequence), already identified in casein genes from other species, likely explain the existence of multiple α_s1-casein isoforms both in SEG/Pas and C57BL/6J strains. Finally, we propose a possible mechanism by which the hallmark tandem duplication of a 18-nt exon (14 copies) may have occurred in the mouse genome.</p

Episodic Occurrence of Favourable Weather Constrains Recovery of a Cold Desert Shrubland After Fire

Key to the long-term resilience of dryland ecosystems is the recovery of foundation plant species following disturbance. In ecosystems with high interannual weather variability, understanding the influence of short-term environmental conditions on establishment of foundation species is essential for identifying vulnerable landscapes and developing restoration strategies. We asked how annual environmental conditions affect post-fire establishment of Artemisia tridentata, a shrub species that dominates landscapes across much of the western United States, and evaluated the influence of episodic establishment on population recovery. We collected A. tridentata stem samples from 33 plots in 12 prescribed fire sites that burned 8–11 years before sampling. We determined individual establishment years using annual growth rings. We measured seasonal soil environmental conditions at the study sites and asked if these conditions predicted annual establishment density. We then evaluated whether establishment patterns could be predicted by site-level climate or dominant subspecies. Finally, we tested the effect of the magnitude and frequency of post-fire establishment episodes on long-term population recovery. Annual post-fire recruitment of A. tridentata was driven by the episodic availability of spring soil moisture. Annual establishment was highest with wetter spring soils (relative influence [RI] = 19.4%) and later seasonal dry-down (RI = 11.8%) in the year of establishment. Establishment density declined greatly 4 to 5 years after fire (RI = 17.1%). Post-fire establishment patterns were poorly predicted by site-level mean climate (marginal R2 ≤ 0.18) and dominant subspecies (marginal R2 ≤ 0.43). Population recovery reflected the magnitude, but not the frequency, of early post-fire establishment pulses. Post-fire A. tridentata density and cover (measured 8–11 years after fire) were more strongly related to the magnitude of the largest establishment pulse than to establishment frequency, suggesting that population recovery may occur with a single favourable establishment year. Synthesis and applications. This study demonstrates the importance of episodic periods of favourable weather for long-term plant population recovery following disturbance. Management strategies that increase opportunities for seed availability to coincide with favourable weather conditions, such as retaining unburned patches or repeated seeding treatments, can improve restoration outcomes in high-priority areas

The Vitamin B1 Metabolism of Staphylococcus aureus Is Controlled at Enzymatic and Transcriptional Levels

Vitamin B1 is in its active form thiamine pyrophosphate (TPP), an essential cofactor for several key enzymes in the carbohydrate metabolism. Mammals must salvage this crucial nutrient from their diet in order to complement the deficiency of de novo synthesis. In the human pathogenic bacterium Staphylococcus aureus, two operons were identified which are involved in vitamin B1 metabolism. The first operon encodes for the thiaminase type II (TenA), 4-amino-5-hydroxymethyl-2-methylpyrimidine kinase (ThiD), 5-(2-hydroxyethyl)-4-methylthiazole kinase (ThiM) and thiamine phosphate synthase (ThiE). The second operon encodes a phosphatase, an epimerase and the thiamine pyrophosphokinase (TPK). The open reading frames of the individual operons were cloned, their corresponding proteins were recombinantly expressed and biochemically analysed. The kinetic properties of the enzymes as well as the binding of TPP to the in vitro transcribed RNA of the proposed operons suggest that the vitamin B1 homeostasis in S. aureus is strongly regulated at transcriptional as well as enzymatic levels