Adapting the multilevel model for estimation of the reliable change index (RCI) with multiple timepoints and multiple sources of error

ObjectiveOne of the primary tools in the assessment of individual‐level patient outcomes is Jacobson and Truax, (1991’s) Reliable Change Index (RCI). Recent efforts to optimize the RCI have revolved around three issues: (a) extending the RCI beyond two timepoints, (b) estimating the RCI using scale scores from item response theory or factor analysis and (c) estimation of person‐ and time‐specific standard errors of measurement.MethodWe present an adaptation of a two‐stage procedure, a measurement error‐corrected multilevel model, as a tool for RCI estimation (with accompanying Statistical Analysis System syntax). Using DASS‐21 data from a community‐based mental health center (N = 379), we illustrate the potential for the model as unifying framework for simultaneously addressing all three limitations in modeling individual‐level RCI estimates.ResultsCompared to the optimal‐fitting RCI model (moderated nonlinear factor analysis scoring with measurement error correction), an RCI model that uses DASS‐21 total scores produced errors in RCI inferences in 50.8% of patients; this was largely driven by overestimation of the proportion of patients with statistically significant improvement.ConclusionEstimation of the RCI can now be enhanced by the use of latent variables, person‐ and time‐specific measurement errors, and multiple timepoints.     

Modulatory effects of adiponectin on the polarization of tumor‐associated macrophages

The plasticity of macrophages with selective functional phenotypes partially arises in respective to their microenvironment. Tumor‐associated macrophages (TAMs) may promote disease progression with tumor specific manner. Here we report that in pediatric malignant soft‐tissue tumors, the presence of TAMs and expression of adiponectin (APN) are heterogeneous. Both APN and TAMs had high expression in rhabdomyosarcoma, especially in the malignant subtype, alveolar rhabdomyosarcoma. To investigate the mode of action of APN on TAM activation, a murine MN/MCA1 sarcoma model was used. The Results revealed that exogenous APN had no effect on MN/MCA1 proliferation but tumor size was markedly reduced in apn^?/? mice versus WT controls. The accumulation of TAMs in apn^?/? mice was also reduced which correlated to downregulated serum levels of MCP‐1. Likewise, TAMs in apn^?/? mice exhibited a M1‐like phenotype, characterized by increase in MHC II^high population and M1 phenotypic markers, such as iNOS gene and serum TNF‐α accompanied by a decrease in M2 markers, namely YM1 gene and serum IL‐10. In addition, APN deficiency increased the number of CD4⁺ T cells, CD8⁺ T cells and NK cells in tumors and reduced tumor metastasis. The altered phenotype of TAMs in apn^?/? mice was associated with a marked decrease in phospho‐p38 and treatment with a p38 MAPK inhibitor significantly reduced tumor size and increased MHC II expression on TAMs in WT mice, implying p38 MAPK signaling pathway may contribute to APN‐mediated TAM polarization. Collectively, our findings suggest that APN may have a potential role in regulating soft tissue sarcoma growth.     

Utility of screening for other causes of infertility in women with "known" polycystic ovary syndrome

We investigated the prevalence of abnormal screening results (questionnaire and testing for other causes of oligo-ovulation, male or tubal factor infertility) in a group of 1,313 oligo-ovulatory women (included and excluded subjects) whose condition was screened for inclusion in the Pregnancy in Polycystic Ovary Syndrome trial, a multicenter clinical trial that was conducted at 13 sites in the United States. Other than failure to demonstrate laboratory evidence of hyperandrogenemia, the most common reasons for subject exclusion were persistent oligospermia and tubal factor infertility.     

Suppression of Anti-Inflammatory Mediators in Metabolic Disease May Be Driven by Overwhelming Pro-Inflammatory Drivers

Obesity is a multifactorial disease and is associated with an increased risk of developing metabolic syndrome and co-morbidities. Dysregulated expansion of the adipose tissue during obesity induces local tissue hypoxia, altered secretory profile of adipokines, cytokines and chemokines, altered profile of local tissue inflammatory cells leading to the development of low-grade chronic inflammation. Low grade chronic inflammation is considered to be the underlying mechanism that increases the risk of developing obesity associated comorbidities. The glucocorticoid induced protein annexin A1 and its N-terminal peptides are anti-inflammatory mediators involved in resolving inflammation. The aim of the current study was to investigate the role of annexin A1 in obesity and associated inflammation. To achieve this aim, the current study analysed data from two feasibility studies in clinical populations: (1) bariatric surgery patients (Pre- and 3 months post-surgery) and (2) Lipodystrophy patients. Plasma annexin A1 levels were increased at 3-months post-surgery compared to pre-surgery (1.2 ± 0.1 ng/mL, n = 19 vs. 1.6 ± 0.1 ng/mL, n = 9, p = 0.009) and positively correlated with adiponectin (p = 0.009, r = 0.468, n = 25). Plasma annexin A1 levels were decreased in patients with lipodystrophy compared to BMI matched controls (0.2 ± 0.1 ng/mL, n = 9 vs. 0.97 ± 0.1 ng/mL, n = 30, p = 0.008), whereas CRP levels were significantly elevated (3.3 ± 1.0 µg/mL, n = 9 vs. 1.4 ± 0.3 µg/mL, n = 31, p = 0.0074). The roles of annexin A1 were explored using an in vitro cell based model (SGBS cells) mimicking the inflammatory status that is observed in obesity. Acute treatment with the annexin A1 N-terminal peptide, AC2-26 differentially regulated gene expression (including PPARA (2.8 ± 0.7-fold, p = 0.0303, n = 3), ADIPOQ (2.0 ± 0.3-fold, p = 0.0073, n = 3), LEP (0.6 ± 0.2-fold, p = 0.0400, n = 3), NAMPT (0.4 ± 0.1-fold, p = 0.0039, n = 3) and RETN (0.1 ± 0.03-fold, p < 0.0001, n = 3) in mature obesogenic adipocytes indicating that annexin A1 may play a protective role in obesity and inflammation. However, this effect may be overshadowed by the continued increase in systemic inflammation associated with rapid tissue expansion in obesity.     

Application of Saliva Inhibition to Detect Underlying Alloantibodies in Bombay Blood Group

IntroductionThe Bombay phenotype is a rare blood group determined by the absence of H antigens. Bombay individuals produce anti-H, a clinically significant antibody that react against all ABO blood group. Anti-H can mask underlying alloantibody during antibody investigation, a challenge in current transfusion practice. The aim of this article is to explore saliva inhibition, a novel method to detect underlying alloantibody in Bombay individuals.Case PresentationThe case is a 93-year-old female transfused with pre-donated autologous blood for a surgery. We determined anti-H subclass and thermal amplitude, secretor status, and optimal ratio of saliva and Bombay plasma. Plasma samples containing anti-H were spiked with anti-Fy(a) to determine the effectiveness of saliva inhibition in uncovering underlying alloantibodies.ResultsAnti-H was confirmed to be predominately IgM with broad thermal amplitude. Tube immediate spin (IS) showed stronger anti-H reactivity compared to column agglutination technology (CAT). Spiked anti-Fy(a) was successfully detected using saliva inhibition method.ConclusionTube IS appears more sensitive to anti-H. Saliva inhibition appears to be a promising method to detect underlying alloantibody in the plasma of Bombay phenotype individuals.     

BrainAGE and regional volumetric analysis of a Buddhist monk: a longitudinal MRI case study

ABSTRACT

Yongey Mingyur Rinpoche (YMR) is a Tibetan Buddhist monk, and renowned meditation practitioner and teacher who has spent an extraordinary number of hours of his life meditating. The brain-aging profile of this expert meditator in comparison to a control population was examined using a machine learning framework, which estimates “brain-age” from brain imaging. YMR’s brain-aging rate appeared slower than that of controls suggesting early maturation and delayed aging. At 41 years, his brain resembled that of a 33-year-old. Specific regional changes did not differentiate YMR from controls, suggesting that the brain-aging differences may arise from coordinated changes spread throughout the gray matter.