Tremor: Clinical Phenomenology and Assessment Techniques

Background: Tremors are among the most common movement disorders. As there can be considerable variability in the manner in which clinicians assess tremor, objective quantitative tools such as electromyography, accelerometry, and computerized, spiral analysis can be very useful in establishing a clinical diagnosis and in research settings. Methods: In this review, we discuss the various methods of quantitative tremor analysis and the classification and pathogenesis of tremor. The most common pathologic tremors and an approach to the diagnosis of tremor etiology are described. Conclusions: Pathologic tremors are common, and the diagnosis of underlying etiology is not always straightforward. Computerized quantitative tremor analysis is a valuable adjunct to careful clinical evaluation in distinguishing tremulous diseases from physiologic tremors, and can also help shed light on their pathogenesis

A temperature-controlled cooling system for accurate quantitative post-mortem MRI

Purpose: To develop a temperature-controlled cooling system to facilitate accurate quantitative post-mortem MRI and enable scanning of unfixed tissue. Methods: A water cooling system was built and integrated with a 7T scanner to minimize temperature drift during MRI scans. The system was optimized for operational convenience and rapid deployment to ensure efficient workflow, which is critical for scanning unfixed post-mortem samples. The performance of the system was evaluated using a 7-h diffusion MRI protocol at 7T with a porcine tissue sample. Quantitative T1, T2, and ADC maps were interspersed with the diffusion scans at seven different time points to investigate the temperature dependence of MRI tissue parameters. The impact of temperature changes on biophysical model fitting of diffusion MRI data was investigated using simulation. Results: Tissue T1, T2, and ADC values remained stable throughout the diffusion MRI scan using the developed cooling system, but varied substantially using a conventional scan setup without temperature control. The cooling system enabled accurate estimation of biophysical model parameters by stabilizing the tissue temperature throughout the diffusion scan, while the conventional setup showed evidence of significantly biased estimation. Conclusion: A temperature-controlled cooling system was developed to tackle the challenge of heating in post-mortem imaging, which shows potential to improve the accuracy and reliability of quantitative post-mortem imaging and enables long scans of unfixed tissue

Structural brain imaging studies offer clues about the effects of the shared genetic etiology among neuropsychiatric disorders

Malalties; GenèticaEnfermedades; GenéticaDiseases; GeneticsGenomewide association studies have found significant genetic correlations among many neuropsychiatric disorders. In contrast, we know much less about the degree to which structural brain alterations are similar among disorders and, if so, the degree to which such similarities have a genetic etiology. From the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) consortium, we acquired standardized mean differences (SMDs) in regional brain volume and cortical thickness between cases and controls. We had data on 41 brain regions for: attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), epilepsy, major depressive disorder (MDD), obsessive compulsive disorder (OCD), and schizophrenia (SCZ). These data had been derived from 24,360 patients and 37,425 controls. The SMDs were significantly correlated between SCZ and BD, OCD, MDD, and ASD. MDD was positively correlated with BD and OCD. BD was positively correlated with OCD and negatively correlated with ADHD. These pairwise correlations among disorders were correlated with the corresponding pairwise correlations among disorders derived from genomewide association studies (r = 0.494). Our results show substantial similarities in sMRI phenotypes among neuropsychiatric disorders and suggest that these similarities are accounted for, in part, by corresponding similarities in common genetic variant architectures

Towards the “Baby Connectome”: Mapping the Structural Connectivity of the Newborn Brain

Defining the structural and functional connectivity of the human brain (the human “connectome”) is a basic challenge in neuroscience. Recently, techniques for noninvasively characterizing structural connectivity networks in the adult brain have been developed using diffusion and high-resolution anatomic MRI. The purpose of this study was to establish a framework for assessing structural connectivity in the newborn brain at any stage of development and to show how network properties can be derived in a clinical cohort of six-month old infants sustaining perinatal hypoxic ischemic encephalopathy (HIE). Two different anatomically unconstrained parcellation schemes were proposed and the resulting network metrics were correlated with neurological outcome at 6 months. Elimination and correction of unreliable data, automated parcellation of the cortical surface, and assembling the large-scale baby connectome allowed an unbiased study of the network properties of the newborn brain using graph theoretic analysis. In the application to infants with HIE, a trend to declining brain network integration and segregation was observed with increasing neuromotor deficit scores

Identification and characterization of a spontaneous ovarian carcinoma in Lewis rats

<p>Abstract</p> <p>Background</p> <p>Ovarian carcinoma is the fourth most common cause of death from cancer in women. Limited progress has been made toward improving the survival rate of patients with this disease in part because of the lack of a good animal model. We present here a model of spontaneous ovarian carcinoma arising in a normal Lewis rat.</p> <p>Methods</p> <p>A spontaneously occurring tumor of the left ovary was found in a normal Lewis rat during necropsy, which was sectioned for histological examination and placed into single cell suspension. Tumor cells were passaged <it>in vivo </it>by intraperitoneal injection into immunocompetent Lewis rats, and <it>in vitro </it>culture resulted in generation of a cell line. Tumor cells were examined by flow cytometry for expression of estrogen receptor α, progesterone receptor, androgen receptor, her-2/neu, epithelial cell adhesion molecule, and CA125. β-catenin expression and cellular localization was assessed by immunocytochemistry. RNA was harvested for gene expression profiling and studying the expression of cytokines.</p> <p>Results</p> <p>The tumor, designated FNAR, could be serially transplanted into Lewis rats and propagated as a cell line <it>in vitro</it>, maintaining the properties of the original tumor. The FNAR cells displayed striking morphologic similarities to human ovarian carcinoma, resembling the endometrioid carcinoma subtype of surface epithelial neoplasms. The cells expressed estrogen receptor α, progesterone receptor, androgen receptor, her-2/neu, epithelial cell adhesion molecule, CA125, and nuclear β-catenin. A gene expression profile showed upregulation of a number of genes that are also upregulated in human ovarian carcinoma.</p> <p>Conclusion</p> <p>This reliable model of ovarian carcinoma should be helpful in better understanding the biology of the disease as well as the development of novel treatment strategies.</p

Engineering High-Fidelity Residue Separations for Selective Harvest

Composition and pretreatment studies of corn stover and wheat stover anatomical fractions clearly show that some corn and wheat stover anatomical fractions are of higher value than others as a biofeedstock. This premise, along with soil sustainability and erosion control concerns, provides the motivation for the selective harvest concept for separating and collecting the higher value residue fractions in a combine during grain harvest. This study recognizes the analysis of anatomical fractions as theoretical feedstock quality targets, but not as practical targets for developing selective harvest technologies. Rather, practical quality targets were established that identified the residue separation requirements of a selective harvest combine. Data are presented that shows that a current grain combine is not capable of achieving the fidelity of residue fractionation established by the performance targets. However, using a virtual engineering approach, based on an understanding of the fluid dynamics of the air stream separation, the separation fidelity can be significantly improved without significant changes to the harvester design. A virtual engineering model of a grain combine was developed and used to perform simulations of the residue separator performance. The engineered residue separator was then built into a selective harvest test combine, and tests performed to evaluate the separation fidelity. Field tests were run both with and without the residue separator installed in the test combine, and the chaff and straw residue streams were collected during harvest of Challis soft white spring wheat. The separation fidelity accomplished both with and without the residue separator was quantified by laboratory screening analysis. The screening results showed that the engineered baffle separator did a remarkable job of effecting high-fidelity separation of the straw and chaff residue streams, improving the chaff stream purity and increasing the straw stream yield

Structural basis for high-affinity binding of LEDGF PWWP to mononucleosomes

Lens epithelium-derived growth factor (LEDGF/p75) tethers lentiviral preintegration complexes (PICs) to chromatin and is essential for effective HIV-1 replication. LEDGF/p75 interactions with lentiviral integrases are well characterized, but the structural basis for how LEDGF/p75 engages chromatin is unknown. We demonstrate that cellular LEDGF/p75 is tightly bound to mononucleosomes (MNs). Our proteomic experiments indicate that this interaction is direct and not mediated by other cellular factors. We determined the solution structure of LEDGF PWWP and monitored binding to the histone H3 tail containing trimethylated Lys36 (H3K36me3) and DNA by NMR. Results reveal two distinct functional interfaces of LEDGF PWWP: a well-defined hydrophobic cavity, which selectively interacts with the H3K36me3 peptide and adjacent basic surface, which non-specifically binds DNA. LEDGF PWWP exhibits nanomolar binding affinity to purified native MNs, but displays markedly lower affinities for the isolated H3K36me3 peptide and DNA. Furthermore, we show that LEDGF PWWP preferentially and tightly binds to in vitro reconstituted MNs containing a tri-methyl-lysine analogue at position 36 of H3 and not to their unmodified counterparts. We conclude that cooperative binding of the hydrophobic cavity and basic surface to the cognate histone peptide and DNA wrapped in MNs is essential for high-affinity binding to chromatin

Ancillary health effects of climate mitigation scenarios as drivers of policy uptake: a review of air quality, transportation and diet co-benefits modeling studies

Background: Significant mitigation efforts beyond the Nationally Determined Commitments (NDCs) coming out of the 2015 Paris Climate Agreement are required to avoid warming of 2 °C above pre-industrial temperatures. Health co-benefits represent selected near term, positive consequences of climate policies that can offset mitigation costs in the short term before the beneficial impacts of those policies on the magnitude of climate change are evident. The diversity of approaches to modeling mitigation options and their health effects inhibits meta-analyses and syntheses of results useful in policy-making. Methods/Design: We evaluated the range of methods and choices in modeling health co-benefits of climate mitigation to identify opportunities for increased consistency and collaboration that could better inform policy-making. We reviewed studies quantifying the health co-benefits of climate change mitigation related to air quality, transportation, and diet published since the 2009 Lancet Commission 'Managing the health effects of climate change' through January 2017. We documented approaches, methods, scenarios, health-related exposures, and health outcomes. Results/Synthesis: Forty-two studies met the inclusion criteria. Air quality, transportation, and diet scenarios ranged from specific policy proposals to hypothetical scenarios, and from global recommendations to stakeholder-informed local guidance. Geographic and temporal scope as well as validity of scenarios determined policy relevance. More recent studies tended to use more sophisticated methods to address complexity in the relevant policy system. Discussion: Most studies indicated significant, nearer term, local ancillary health benefits providing impetus for policy uptake and net cost savings. However, studies were more suited to describing the interaction of climate policy and health and the magnitude of potential outcomes than to providing specific accurate estimates of health co-benefits. Modeling the health co-benefits of climate policy provides policy-relevant information when the scenarios are reasonable, relevant, and thorough, and the model adequately addresses complexity. Greater consistency in selected modeling choices across the health co-benefits of climate mitigation research would facilitate evaluation of mitigation options particularly as they apply to the NDCs and promote policy uptake

Update to the study protocol for an implementation-effectiveness trial comparing two education strategies for improving the uptake of noninvasive ventilation in patients with severe COPD exacerbation

BACKGROUND: There is strong evidence that noninvasive ventilation (NIV) improves the outcomes of patients hospitalized with severe COPD exacerbation, and NIV is recommended as the first-line therapy for these patients. Yet, several studies have demonstrated substantial variation in NIV use across hospitals, leading to preventable morbidity and mortality. In addition, prior studies suggested that efforts to increase NIV use in COPD need to account for the complex and interdisciplinary nature of NIV delivery and the need for team coordination. Therefore, our initial project aimed to compare two educational strategies: online education (OLE) and interprofessional education (IPE), which targets complex team-based care in NIV delivery. Due to the impact of the COVID-19 pandemic on recruitment and planned intervention, we had made several changes in the study design, statistical analysis, and implementation strategies delivery as outlined in the methods. METHODS: We originally proposed a two-arm, pragmatic, cluster, randomized hybrid implementation-effectiveness trial comparing two education strategies to improve NIV uptake in patients with severe COPD exacerbation in 20 hospitals with a low baseline rate of NIV use. Due to logistical constrains and slow recruitment, we changed the study design to an opened cohort stepped-wedge design with three steps which will allow the institutions to enroll when they are ready to participate. Only the IPE strategy will be implemented, and the education will be provided in an online virtual format. Our primary outcome will be the hospital-level risk-standardized NIV proportion for the period post-IPE training, along with the change in rate from the period prior to training. Aim 1 will compare the change over time of NIV use among patients with COPD in the step-wedged design. Aim 2 will explore the mediators\u27 role (respiratory therapist autonomy and team functionality) on the relationship between the implementation strategies and effectiveness. Finally, in Aim 3, through interviews with providers, we will assess the acceptability and feasibility of the educational training. CONCLUSION: The changes in study design will result in several limitation. Most importantly, the hospitals in the three cohorts are not randomized as they enroll based on their readiness. Second, the delivery of the IPE is virtual, and it is not known if remote education is conducive to team building. However, this study will be among the first to test the impact of IPE in the inpatient setting carefully and may generalize to other interventions directed to seriously ill patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT04206735 . Registered on December 20, 2019