Inter-rater reliability of the Dysexecutive Questionnaire (DEX): comparative data from non-clinician respondents – all raters are not equal

Primary objective: The Dysexecutive Questionnaire (DEX) is used to obtain information about executive and emotional problems after neuropathology. The DEX is self-completed by the patient (DEX-S) and an independent rater such as a family member (DEX-I). This study examined the level of inter-rater agreement between either two or three non-clinician raters on the DEX-I in order to establish the reliability of DEX-I ratings. Methods and procedures: Family members and/or carers of 60 people with mixed neuropathology completed the DEX-I. For each patient, DEX-I ratings were obtained from either two or three raters who knew the person well prior to brain injury. Main outcomes and results: We obtained two independent-ratings for 60 patients and three independent-ratings for 36 patients. Intra-class correlations revealed that there was only a modest level of agreement for items, subscale and total DEX scores between raters for their particular family member. Several individual DEX items had low reliability and ratings for the emotion sub-scale had the lowest level of agreement. Conclusions: Independent DEX ratings completed by two or more non-clinician raters show only moderate correlation. Suggestions are made for improving the reliability of DEX-I ratings.</p

Expression of Mo3e antigen by cultured human umbilical vein endothelial cells (HUVEC) stimulated by phorbol myristate acetate (PMA) and related pharmacological inducers of protein kinase C

Mo3e is a protease-sensitive membrane antigen (p75,50) selectively expressed by human monocytic cells (monocytes and U-937 cells) stimulated in vitro by exposure to a variety of activating factors, including phorbol diester compounds, bacterial lipopolysaccharide (LPS), and muramyl dipeptide (MDP) (R. F. Todd et al., J. Immunol. 135, 3869, 1985). Here we report that primary and multiply-passaged cultures of HUVEC also express the Mo3e determinant after stimulation by phorbol myristate acetate (PMA) and related inducers of protein kinase C. As measured in a radioimmunoassay of anti-Mo3e antibody binding to monolayer cultures of HUVEC, unstimulated cells bore little if any Mo3e. After culture for 4-120 hr in medium containing PMA, 4[beta]-phorbol dibutyrate, 4[beta]-phorbol didecanoate, or mezerein (each at a conentration of 81 nM), or 1-oleoyl-2-acetoyl-sn-3-glycerol (1 mM), HUVEC were found to selectively express the Mo3e determinant. The magnitude of expression was dependent upon the concentration of the stimulus, maximal by 24 hr, and inhibited by cycloheximide. The combination of PMA and the calcium ionophore, ionomycin, had an additive or synergistic effect on HUVEC Mo3e expression. The biologically inactive phorbol compounds 4[beta]-phorbol and 4[alpha]-phorbol didecanoate failed to stimulate Mo3e expression. Also inactive as inducers of HUVEC Mo3e expression were crude lymphokine and monokine supernatants, recombinant human lymphokines (interferon-[gamma] and interleukin-2), recombinant human monokines (interleukin-1 and tumor necrosis factor), bacterial cell wall products including LPS and MDP, pharmacologic agents that increase intracellular cyclic adenosine monophosphate (prostaglandin E2, cholera toxin, theophylline, isoproterenol and isobutylmethylxanthine), lectins (Con A and PHA), and heparin. These results indicate that Mo3e is an inducible plasma membrane antigen of not only mononuclear phagocytes but also cultured HUVEC.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27376/1/0000404.pd

Development of Competency-based Online Genomic Medicine Training (COGENT)

The fields of genetics and genomics have greatly expanded across medicine through the development of new technologies that have revealed genetic contributions to a wide array of traits and diseases. Thus, the development of widely available educational resources for all healthcare providers is essential to ensure the timely and appropriate utilization of genetics and genomics patient care. In 2020, the National Human Genome Research Institute released a call for new proposals to develop accessible, sustainable online education for health providers. This paper describes the efforts of the six teams awarded to reach the goal of providing genetic and genomic training modules that are broadly available for busy clinicians

Ellipsoidal analysis of coordination polyhedra

The idea of the coordination polyhedron is essential to understanding chemical structure. Simple polyhedra in crystalline compounds are often deformed due to structural complexity or electronic instabilities so distortion analysis methods are useful. Here we demonstrate that analysis of the minimum bounding ellipsoid of a coordination polyhedron provides a general method for studying distortion, yielding parameters that are sensitive to various orders in metal oxide examples. Ellipsoidal analysis leads to discovery of a general switching of polyhedral distortions at symmetry-disallowed transitions in perovskites that may evidence underlying coordination bistability, and reveals a weak off-centre ‘d(5) effect' for Fe(3+) ions that could be exploited in multiferroics. Separating electronic distortions from intrinsic deformations within the low temperature superstructure of magnetite provides new insights into the charge and trimeron orders. Ellipsoidal analysis can be useful for exploring local structure in many materials such as coordination complexes and frameworks, organometallics and organic molecules

Dissociating Profiles of Social Cognitive Disturbances Between Mixed Personality and Anxiety Disorder.

Background:An emerging body of research has begun to elucidate disturbances to social cognition in specific personality disorders (PDs). No research has been conducted on patients with Mixed Personality Disorder (MPD), however, who meet multiple diagnostic criteria. Further, very few studies have compared social cognition between patients with PD and those presenting with symptomatic diagnoses that co-occur with personality pathologies, such as anxiety disorder (AD). The aim of this study was to provide a detailed characterization of deficits to various aspects of social cognition in MPD and dissociate impairments specific to MPD from those exhibited by patients with AD who differ in the severity of personality pathology. Method:Building on our previous research, we administered a large battery of self-report and performance-based measures of social cognition to age-, sex- and education-matched groups of patients with MPD or AD, and healthy control participants (HCs; n = 29, 23, and 54, respectively). This permitted a detailed profiling of these clinical groups according to impairments in emotion recognition and regulation, imitative control, low-level visual perspective taking, and empathic awareness and expression. Results:The MPD group demonstrated poorer emotion recognition for negative facial expressions relative to both HCs and AD. Compared with HCs, both clinical groups also performed significantly worse in visual perspective taking and interference resolution, and reported higher personal distress when empathizing and more state-oriented emotion regulation. Conclusion:We interpret our results to reflect dysfunctional cognitive control that is common to patients with both MPD and AD. Given the patterns of affective dispositions that characterize these two diagnostic groups, we suggest that prolonged negative affectivity is associated with inflexible styles of emotion regulation and attribution. This might potentiate the interpersonal dysfunction exhibited in MPD, particularly in negatively valenced and challenging social situations

Oscillatory activity in prefrontal and posterior regions during implicit letter-location binding.

Many cognitive abilities involve the integration of information from different modalities, a process referred to as “binding.” It remains less clear, however, whether the creation of bound representations occurs in an involuntary manner, and whether the links between the constituent features of an object are symmetrical. We used magnetoencephalography to investigate whether oscillatory brain activity related to binding processes would be observed in conditions in which participants maintain one feature only (involuntary binding); and whether this activity varies as a function of the feature attended to by participants (binding asymmetry). Participants performed two probe recognition tasks that were identical in terms of their perceptual characteristics and only differed with respect to the instructions given (to memorize either consonants or locations). MEG data were reconstructed using a current source distribution estimation in the classical frequency bands. We observed implicit verbal–spatial binding only when participants successfully maintained the identity of consonants, which was associated with a selective increase in oscillatory activity over prefrontal regions in all frequency bands during the first half of the retention period and accompanied by increased activity in posterior brain regions. The increase in oscillatory activity in prefrontal areas was only observed during the verbal task, which suggests that this activity might be signaling neural processes specifically involved in cross-code binding. Current results are in agreement with proposals suggesting that the prefrontal cortex function as a “pointer” which indexes the features that belong together within an object

DC-SIGN(+) Macrophages Control the Induction of Transplantation Tolerance

Tissue effector cells of the monocyte lineage can differentiate into different cell types with specific cell function depending on their environment. The phenotype, developmental requirements, and functional mechanisms of immune protective macrophages that mediate the induction of transplantation tolerance remain elusive. Here, we demonstrate that costimulatory blockade favored accumulation of DC-SIGN-expressing macrophages that inhibited CD8(+) T cell immunity and promoted CD4(+)Foxp3(+) Treg cell expansion in numbers. Mechanistically, that simultaneous DC-SIGN engagement by fucosylated ligands and TLR4 signaling was required for production of immunoregulatory IL-10 associated with prolonged allograft survival. Deletion of DC-SIGN-expressing macrophages in vivo, interfering with their CSF1-dependent development, or preventing the DC-SIGN signaling pathway abrogated tolerance. Together, the results provide new insights into the tolerogenic effects of costimulatory blockade and identify DC-SIGN(+) suppressive macrophages as crucial mediators of immunological tolerance with the concomitant therapeutic implications in the clinic.This work was supported by the COST Action BM1305: Action to Focus and Accelerate Cell Tolerogenic Therapies (A FACTT), the Mount Sinai Recanati/Miller Transplantation Institute developmental funds, AST/Pfizer Basic Science Faculty Development Grant, Ministerio de Educacióny Ciencia SAF2010-15062, SAF2013-48834-R, and Fundación Mutua Madrileñ a grants to J.O. A portion of this work appears as part of the doctoral thesis of P.C.S

Premature ovarian failure and ovarian autoimmunity

Premature ovarian failure (POF) is defined as a syndrome characterized by menopause before the age of 40 yr. The patients suffer from anovulation and hypoestrogenism. Approximately 1% of women will experience menopause before the age of 40 yr. POF is a heterogeneous disorder with a multicausal pathogenesis involving chromosomal, genetic, enzymatic, infectious, and iatrogenic causes. There remains, however, a group of POF patients without a known etiology, the so-called "idiopathic" form. An autoimmune etiology is hypothesized for the POF cases with a concomitant Addison's disease and/or oophoritis. It is concluded in this review that POF in association with adrenal autoimmunity and/or Addison's disease (2-10% of the idiopathic POF patients) is indeed an autoimmune disease. The following evidence warrants this view: 1) The presence of autoantibodies to steroid-producing cells in these patients; 2) The characterization of shared autoantigens between adrenal and ovarian steroid-producing cells; 3) The histological picture of the ovaries of such cases (lymphoplasmacellular infiltrate around steroid-producing cells); 4) The existence of various autoimmune animal models for this syndrome, which underlines the autoimmune nature of the disease. There is some circumstantial evidence for an autoimmune pathogenesis in idiopathic POF patients in the absence of adrenal autoimmunity or Addison's disease. Arguments in support of this are: 1) The presence of cellular immune abnormalities in this POF patient group reminiscent of endocrine autoimmune diseases such as IDDM, Graves' disease, and Addison's disease; 2) The more than normal association with IDDM and myasthenia gravis. Data on the presence of various ovarian autoantibodies and anti-receptor antibodies in these patients are, however, inconclusive and need further evaluation. A strong argument against an autoimmune pathogenesis of POF in these patients is the nearly absent histological confirmation (the presence of an oophoritis) in these cases (< 3%). However, in animal models using ZP immunization, similar follicular depletion and fibrosis (as in the POF women) can be detected. Accepting the concept that POF is a heterogenous disorder in which some of the idiopathic forms are based on an abnormal self-recognition by th

Global Patterns and Controls of Nutrient Immobilization On Decomposing Cellulose In Riverine Ecosystems

Microbes play a critical role in plant litter decomposition and influence the fate of carbon in rivers and riparian zones. When decomposing low-nutrient plant litter, microbes acquire nitrogen (N) and phosphorus (P) from the environment (i.e., nutrient immobilization), and this process is potentially sensitive to nutrient loading and changing climate. Nonetheless, environmental controls on immobilization are poorly understood because rates are also influenced by plant litter chemistry, which is coupled to the same environmental factors. Here we used a standardized, low-nutrient organic matter substrate (cotton strips) to quantify nutrient immobilization at 100 paired stream and riparian sites representing 11 biomes worldwide. Immobilization rates varied by three orders of magnitude, were greater in rivers than riparian zones, and were strongly correlated to decomposition rates. In rivers, P immobilization rates were controlled by surface water phosphate concentrations, but N immobilization rates were not related to inorganic N. The N:P of immobilized nutrients was tightly constrained to a molar ratio of 10:1 despite wide variation in surface water N:P. Immobilization rates were temperature-dependent in riparian zones but not related to temperature in rivers. However, in rivers nutrient supply ultimately controlled whether microbes could achieve the maximum expected decomposition rate at a given temperature