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Background: In institutional dementia care, person-centered care improves care processes and the quality of life of residents. However, communication gaps impede the implementation of person-centered care in favor of routinized care., Objective: We evaluated whether self-organizing knowledge management reduces communication gaps and improves the quality of person-centered dementia care., Method: We implemented a self-organizing knowledge management system. Eight significant others of residents with severe dementia and six professional caregivers used a mobile application for six months. We conducted qualitative interviews and focus groups afterward., Main Findings: Participants reported that the system increased the quality of person-centered care, reduced communication gaps, increased the task satisfaction of caregivers and the wellbeing of significant others., Conclusions: Based on our findings, we develop the following hypotheses: self-organizing knowledge management might provide a promising tool to improve the quality of person-centered care. It might reduce communication barriers that impede person-centered care. It might allow transferring content-maintaining tasks from caregivers to significant others. Such distribution of tasks, in turn, might be beneficial for both parties. Furthermore, shared knowledge about situational features might guide person-centered interventions., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: The aim of this study was to determine whether downstream [peroxisome proliferator-activated-receptor alpha (PPARα) and the G-protein coupled receptor, GPR119] and upstream (a fatty acid translocase, CD36) signaling targets of N-oleoylethanolamide (OEA) were necessary for weight loss, metabolic improvements, and diet preference following vertical sleeve gastrectomy (VSG)., Summary Background Data: OEA is an anorectic N-acylethanolamine produced from dietary fats within the intestinal lumen that can modulate lipid metabolism, insulin secretion, and energy expenditure by activating targets such as PPARα and GPR119., Methods: Diet-induced obese mice, including wild-type or whole body knockout (KO) of PPARα, GPR119, and CD36, were stratified to either VSG or sham surgery before body weight, body composition, diet preference, and glucose and lipid metabolic endpoints were assessed., Results: We found increased duodenal production of OEA and expression of both GPR119 and CD36 were upregulated in wild-type mice after VSG. However, weight loss and glucose tolerance were improved in response to VSG in PPARαKO, GPR119KO, and CD36KO mice. In fact, VSG corrected hepatic triglyceride dysregulation in CD36KO mice, and circulating triglyceride and cholesterol levels in PPARαKO mice. Lastly, we found PPARα-mediated signaling contributes to macronutrient preference independent of VSG, while removal of CD36 signaling blunts the VSG-induced shift toward carbohydrate preference., Conclusions: In the search for more effective and less invasive therapies to help reverse the global acceleration of obesity and obesity-related disease OEA is a promising candidate; however, our data indicate that it is not an underlying mechanism of the effectiveness of VSG.

We investigated the role of copy number alterations to refine risk stratification in adult Philadelphia chromosome positive (Ph) + acute lymphoblastic leukemia (ALL) treated with tyrosine kinase inhibitors (TKIs) and allogeneic stem cell transplantation (aSCT). Ninety-seven Ph + ALL patients (median age 41 years; range 18-64 years) within the prospective multicenter German Multicenter ALL Study Group studies 06/99 (n = 8) and 07/2003 (n = 89) were analyzed. All patients received TKI and aSCT in first complete remission (CR1). Copy number analysis was performed with single nucleotide polymorphism arrays and validated by multiplex ligation-dependent probe amplification. The frequencies of recurrently deleted genes were: IKZF1, 76%; CDKN2A/2B, 45%; PAX5, 43%; BTG1, 18%; EBF1, 13%; ETV6, 5%; RB, 14%. In univariate analyses, the presence of CDKN2A/2B deletions had a negative impact on all endpoints: overall survival ( P = .023), disease-free survival ( P = .012), and remission duration ( P = .036). The negative predictive value of CDKN2A/2B deletions was retained in multivariable analysis along with other factors such as timing of TKI therapy, intensity of conditioning, achieving remission after induction phase 1 and BTG1 deletions. We therefore conclude that acquired genomic CDKN2A/2B deletions identify a subgroup of Ph + ALL patients, who have an inferior prognosis despite aSCT in CR1. Their poor outcome was attributable primarily to a high relapse rate after aSCT., (© 2018 by The American Society of Hematology.)

Background: The first 2 years of a child's life are a particularly critical time period for obesity prevention., Aim: An increasing amount of research across the world is aimed at understanding factors that impact early childhood obesity and developing interventions that target these factors effectively. With this growing interest, new and interdisciplinary research teams are developing to meet this research need. Due to rapid growth velocity during this phase of the lifespan, typical assessments used in older populations may not be valid or applicable in infants, and investigators need to be aware of the pros and cons of specific methodological strategies., Methods: This paper provides an overview of methodology available to assess obesity-related factors in the areas of anthropometry and body composition, nutrient intake, and energy expenditure in infants aged 0-2 years., Results: Gold standard measures for body composition, such as dual-energy X-ray absorptiometry (DXA) or other imaging techniques, are costly, require highly trained personnel, and are limited for research application. Nutrient intake methodology primarily includes surveys and questionnaires completed via parent proxy report. In terms of energy expenditure, methods of calorimetry are expensive and may not differentiate between different activities. Questionnaires or physical activity sensors offer another way of energy expenditure assessment. However, questionnaires have a certain recall bias, while the sensors require further validation., Conclusions: Overall, in addition to understanding the pros and cons of each assessment tool, researchers should take into consideration the experience of the interdisciplinary team of investigators, as well as the cost and availability of measures at their institution.

Background: Cytogenetic aberrations such as deletion of chromosome 5q (del(5q)) represent key elements in routine clinical diagnostics of haematological malignancies. Currently established methods such as metaphase cytogenetics, FISH or array-based approaches have limitations due to their dependency on viable cells, high costs or semi-quantitative nature. Importantly, they cannot be used on low abundance DNA. We therefore aimed to establish a robust and quantitative technique that overcomes these shortcomings., Methods: For precise determination of del(5q) cell fractions, we developed an inexpensive multiplex-PCR assay requiring only nanograms of DNA that simultaneously measures allelic imbalances of 12 independent short tandem repeat markers., Results: Application of this method to n=1142 samples from n=260 individuals revealed strong intermarker concordance (R²=0.77-0.97) and reproducibility (mean SD: 1.7%). Notably, the assay showed accurate quantification via standard curve assessment (R²>0.99) and high concordance with paired FISH measurements (R²=0.92) even with subnanogram amounts of DNA. Moreover, cytogenetic response was reliably confirmed in del(5q) patients with myelodysplastic syndromes treated with lenalidomide. While the assay demonstrated good diagnostic accuracy in receiver operating characteristic analysis (area under the curve: 0.97), we further observed robust correlation between bone marrow and peripheral blood samples (R²=0.79), suggesting its potential suitability for less-invasive clonal monitoring., Conclusions: In conclusion, we present an adaptable tool for quantification of chromosomal aberrations, particularly in problematic samples, which should be easily applicable to further tumour entities., Competing Interests: Competing interests: CH declares part ownership of the MLL Munich Leukemia Laboratory GmbH., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Clonal evolution is believed to be a main driver for progression of various types of cancer and implicated in facilitating resistance to drugs. However, the hierarchical organization of malignant clones in the hematopoiesis of myelodysplastic syndromes (MDS) and its impact on response to drug therapy remain poorly understood. Using high-throughput sequencing of patient and xenografted cells, we evaluated the intratumoral heterogeneity (n= 54) and reconstructed mutational trajectories (n = 39) in patients suffering from MDS (n = 52) and chronic myelomonocytic leukemia-1 (n = 2). We identified linear and also branching evolution paths and confirmed on a patient-specific level that somatic mutations in epigenetic regulators and RNA splicing genes frequently constitute isolated disease-initiating events. Using high-throughput exome- and/or deep-sequencing, we analyzed 103 chronologically acquired samples from 22 patients covering a cumulative observation time of 75 years MDS disease progression. Our data revealed highly dynamic shaping of complex oligoclonal architectures, specifically upon treatment with lenalidomide and other drugs. Despite initial clinical response to treatment, patients' marrow persistently remained clonal with rapid outgrowth of founder-, sub-, or even fully independent clones, indicating an increased dynamic rate of clonal turnover. The emergence and disappearance of specific clones frequently correlated with changes of clinical parameters, highlighting their distinct and far-reaching functional properties. Intriguingly, increasingly complex mutational trajectories are frequently accompanied by clinical progression during the course of disease. These data substantiate a need for regular broad molecular monitoring to guide clinical treatment decisions in MDS., (© 2016 by The American Society of Hematology.)