456 research outputs found

    Development of a Clinician Report Measure to Assess Psychotherapy for Depression in Usual Care Settings

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    Although mental health policy initiatives have called for quality improvement in depression care, practical tools to describe the quality of psychotherapy for depression are not available. We developed a clinician-report measure of adherence to three types of psychotherapy for depression—cognitive behavioral therapy, interpersonal therapy, and psychodynamic therapy. A total of 727 clinicians from a large, national managed behavioral health care organization responded to a mail survey. The measure demonstrated good psychometric properties, including appropriate item-scale correlations, internal consistency reliability, and a three-factor structure. Our results suggest that this questionnaire may be a promising approach to describing psychotherapy for depression in usual care

    Regenerative Medicine and the Developing World

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    This is the first study to systematically identify and prioritize which applications of regenerative medicine are the most promising for improving health in developing countries

    Molecular estimation of neurodegeneration pseudotime in older brains.

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    The temporal molecular changes that lead to disease onset and progression in Alzheimer\u27s disease (AD) are still unknown. Here we develop a temporal model for these unobserved molecular changes with a manifold learning method applied to RNA-Seq data collected from human postmortem brain samples collected within the ROS/MAP and Mayo Clinic RNA-Seq studies. We define an ordering across samples based on their similarity in gene expression and use this ordering to estimate the molecular disease stage-or disease pseudotime-for each sample. Disease pseudotime is strongly concordant with the burden of tau (Braak score, P = 1.0 × 10-5), Aβ (CERAD score, P = 1.8 × 10-5), and cognitive diagnosis (P = 3.5 × 10-7) of late-onset (LO) AD. Early stage disease pseudotime samples are enriched for controls and show changes in basic cellular functions. Late stage disease pseudotime samples are enriched for late stage AD cases and show changes in neuroinflammation and amyloid pathologic processes. We also identify a set of late stage pseudotime samples that are controls and show changes in genes enriched for protein trafficking, splicing, regulation of apoptosis, and prevention of amyloid cleavage pathways. In summary, we present a method for ordering patients along a trajectory of LOAD disease progression from brain transcriptomic data

    A solution of the coincidence problem based on the recent galactic core black hole mass density increase

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    A mechanism capable to provide a natural solution to two major cosmological problems, i.e. the cosmic acceleration and the coincidence problem, is proposed. A specific brane-bulk energy exchange mechanism produces a total dark pressure, arising when adding all normal to the brane negative pressures in the interior of galactic core black holes. This astrophysically produced negative dark pressure explains cosmic acceleration and why the dark energy today is of the same order to the matter density for a wide range of the involved parameters. An exciting result of the analysis is that the recent rise of the galactic core black hole mass density causes the recent passage from cosmic deceleration to acceleration. Finally, it is worth mentioning that this work corrects a wide spread fallacy among brane cosmologists, i.e. that escaping gravitons result to positive dark pressure.Comment: 14 pages, 3 figure

    Human embryonic stem cell-derived cardiomyocyte platform screens inhibitors of SARS-CoV-2 infection.

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    Patients with cardiovascular comorbidities are more susceptible to severe infection with SARS-CoV-2, known to directly cause pathological damage to cardiovascular tissue. We outline a screening platform using human embryonic stem cell-derived cardiomyocytes, confirmed to express the protein machinery critical for SARS-CoV-2 infection, and a SARS-CoV-2 spike-pseudotyped virus system. The method has allowed us to identify benztropine and DX600 as novel inhibitors of SARS-CoV-2 infection in a clinically relevant stem cell-derived cardiomyocyte line. Discovery of new medicines will be critical for protecting the heart in patients with SARS-CoV-2, and for individuals where vaccination is contraindicated

    Bridging the rodent to human translational gap: Marmosets as model systems for the study of Alzheimer\u27s disease.

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    INTRODUCTION: Our limited understanding of the mechanisms that trigger the emergence of Alzheimer\u27s disease (AD) has contributed to the lack of interventions that stop, prevent, or fully treat this disease. We believe that the development of a non-human primate model of AD will be an essential step toward overcoming limitations of other model systems and is crucial for investigating primate-specific mechanisms underlying the cellular and molecular root causes of the pathogenesis and progression of AD. METHODS: A new consortium has been established with funding support from the National Institute on Aging aimed at the generation, characterization, and validation of Marmosets As Research Models of AD (MARMO-AD). This consortium will study gene-edited marmoset models carrying genetic risk for AD and wild-type genetically diverse aging marmosets from birth throughout their lifespan, using non-invasive longitudinal assessments. These include characterizing the genetic, molecular, functional, behavioral, cognitive, and pathological features of aging and AD. RESULTS: The consortium successfully generated viable founders carrying DISCUSSION: By establishing marmoset models of AD, we will be able to investigate primate-specific cellular and molecular root causes that underlie the pathogenesis and progression of AD, overcome limitations of other model organisms, and support future translational studies to accelerate the pace of bringing therapies to patients

    Phenotypic Plasticity of Leaf Shape along a Temperature Gradient in Acer rubrum

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    Both phenotypic plasticity and genetic determination can be important for understanding how plants respond to environmental change. However, little is known about the plastic response of leaf teeth and leaf dissection to temperature. This gap is critical because these leaf traits are commonly used to reconstruct paleoclimate from fossils, and such studies tacitly assume that traits measured from fossils reflect the environment at the time of their deposition, even during periods of rapid climate change. We measured leaf size and shape in Acer rubrum derived from four seed sources with a broad temperature range and grown for two years in two gardens with contrasting climates (Rhode Island and Florida). Leaves in the Rhode Island garden have more teeth and are more highly dissected than leaves in Florida from the same seed source. Plasticity in these variables accounts for at least 6–19 % of the total variance, while genetic differences among ecotypes probably account for at most 69–87 %. This study highlights the role of phenotypic plasticity in leaf-climate relationships. We suggest that variables related to tooth count and leaf dissection in A. rubrum can respond quickly to climate change, which increases confidence in paleoclimate methods that use these variables
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