Inflammation Combined with Ischemia Produces Myelin Injury and Plaque-Like Aggregates of Myelin, Amyloid-β and AβPP in Adult Rat Brain.

BackgroundIschemia, white matter injury, and Alzheimer's disease (AD) pathologies often co-exist in aging brain. How one condition predisposes to, interacts with, or perhaps causes the others remains unclear.ObjectivesTo better understand the link between ischemia, white matter injury, and AD, adult rats were administered lipopolysaccharide (LPS) to serve as an inflammatory stimulus, and 24 h later subjected to 20-min focal cerebral ischemia (IS) followed by 30-min hypoxia (H).MethodsMyelin and axonal damage, as well as amyloid-β (Aβ) and amyloid-β protein precursor (AβPP) deposition were examined by Western blot and immunocytochemistry following LPS/IS/H. Findings were compared to the 5XFAD mouse AD brain.ResultsMyelin/axonal injury was observed bilaterally in cortex following LPS/IS/H, along with an increase in IL-1, granzyme B, and LPS. AβPP deposition was present in ischemic striatum in regions of myelin loss. Aβ(1-42) and AβPP were deposited in small foci in ischemic cortex that co-localized with myelin aggregates. In the 5XFAD mouse AD model, cortical amyloid plaques also co-localized with myelin aggregates.ConclusionsLPS/IS/H produce myelin injury and plaque-like aggregates of myelin. AβPP and Aβ co-localize with these myelin aggregates

Electronic Clinical Quality Measures of Health Information Technology and Hospital Performance: Evidence of U.S. Hospitals

Electronic clinical quality measures (eCQMs) are an integral part of health information technology (HIT). This study explores the effect of eCQM implementation on hospital performance. The study proposes hospital profitability, efficiency, and quality to measure hospital performance. Based on the literature, this research hypothesizes that implementing eCQMs would positively impact hospital profitability, efficiency, and quality. The sample data are drawn from the 2017 American Hospital Association (AHA) U.S. Hospital Survey datasets (N = 6282), the 2017 AHA U.S. Hospital I.T. Survey dataset (N = 3451), and the 2017 Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) datasets (N = 4345). This paper also analyzes the effect of four control variables in the profitablity models – hospital bed size, location, ownership, and teaching status. The study uses multiple regression models to test the hypotheses. Data strongly supports Hypothesis 1 (profitability), moderately supports Hypothesis 2 (efficiency), and does not support Hypothesis 3 (quality). Control variables show mixed results. Both theoretical and practical implications are discussed. Implications and future directions for this research shed light on the potential benefits of implementing eCQMs in hospitals

Hypogastric artery bypass to preserve pelvic circulation: improved outcome after endovascular abdominal aortic aneurysm repair

AbstractObjectiveThis study was carried out to compare the functional outcomes after hypogastric artery bypass and coil embolization for management of common iliac artery aneurysms in the endovascular repair of aortoiliac aneurysms (EVAR).MethodsBetween 1996 and 2002, 265 patients underwent elective or emergent EVAR. Data were retrospectively reviewed for 21 (8%) patients with iliac artery aneurysms 25 mm or larger that involved the iliac bifurcation. Patients underwent hypogastric artery bypass (n = 9) or coil embolization (n = 12). Interviews about past and current levels of activity were conducted. A disability score (DS) was quantitatively graded on a discrete scale ranging from 0 to 10, corresponding to “virtually bed-bound” to exercise tolerance “greater than a mile.” Worsening or improvement of symptoms was expressed as a difference in DS between two time points (-, worsening; +, improvement).ResultsThere was no difference in age (72.6 ± 7.3 years vs 73.1 ± 6.4 years), sex (male-female ratio, 8:1 vs 11:1), abdominal aortic aneurysm size (60.1 ± 5.9 mm vs 59.3 ± 7.0 mm), or number of preoperative comorbid conditions (1.9 ± 0.8 vs 2.1 ± 0.8) between hypogastric bypass and coil embolization groups, respectively. Mean follow-up was shorter after hypogastric bypass (14.8 vs 20.5 months; P < .05). There was no difference in the mean overall baseline DS between the bypass and the embolization groups (8.0 vs 7.8). Six (50%) of the 12 patients with coil embolization reported symptoms of buttock claudication ipsilateral to the occluded hypogastric artery. No symptoms of buttock claudication were reported after hypogastric bypass (P < .05). There was a decrease in the DS after both procedures; however, coil embolization was associated with a significantly worse DS compared with hypogastric artery bypass (4.5 vs 7.3; P < .001). In 4 (67%) of 6 patients with claudication after coil embolization symptoms improved, with a DS of 5.4 at last follow-up. This was significantly worse than in patients undergoing hypogastric artery bypass, with a DS of 7.8 at last follow-up (P < .001). There was no difference between the groups in duration of procedure, blood loss, length of hospital stay, morbidity, or mortality (0%).ConclusionsHypogastric artery bypass to preserve pelvic circulation is safe, and significantly decreases the risk for buttock claudication. Preservation of pelvic circulation results in significant improvement in the ambulatory status of patients with common iliac artery aneurysms, compared with coil embolization

Cdk5rap2 Interacts with Pericentrin to Maintain the Neural Progenitor Pool in the Developing Neocortex

Primary autosomal-recessive microcephaly (MCPH) and Majewski osteodysplastic primordial dwarfism type II (MOPDII) are both genetic diseases that result in decreased brain size at birth. MCPH is thought to arise from alterations in the size of the neural progenitor pool, but the cause of this defect has not been thoroughly explored. We find that one of the genes associated with MCPH, Cdk5rap2, is highly expressed in the neural progenitor pool and that its loss results in a depletion of apical progenitors and increased cell-cycle exit leading to premature neuronal differentiation. We link Cdk5rap2 function to the pericentriolar material protein pericentrin, loss of function of which is associated with MOPDII. Depletion of pericentrin in neural progenitors phenocopies effects of Cdk5rap2 knockdown and results in decreased recruitment of Cdk5rap2 to the centrosome. Our findings uncover a common mechanism, involving aberrations in the neurogenesis program, that may underlie the development of microcephaly in multiple diseases.National Institutes of Health (U.S.) (grant NS37007)Howard Hughes Medical Institute (Investigator

toward modeling kinetics of biomolecular complexes

In order to advance the mission of in silico cell biology, modeling the interactions of large and complex biological systems becomes increasingly relevant. The combination of molecular dynamics (MD) and Markov state models (MSMs) have enabled the construction of simplified models of molecular kinetics on long timescales. Despite its success, this approach is inherently limited by the size of the molecular system. With increasing size of macromolecular complexes, the number of independent or weakly coupled subsystems increases, and the number of global system states increase exponentially, making the sampling of all distinct global states unfeasible. In this work, we present a technique called Independent Markov Decomposition (IMD) that leverages weak coupling between subsystems in order to compute a global kinetic model without requiring to sample all combinatorial states of subsystems. We give a theoretical basis for IMD and propose an approach for finding and validating such a decomposition. Using empirical few-state MSMs of ion channel models that are well established in electrophysiology, we demonstrate that IMD can reproduce experimental conductance measurements with a major reduction in sampling compared with a standard MSM approach. We further show how to find the optimal partition of all-atom protein simulations into weakly coupled subunits

Genome of Drosophila suzukii, the spotted wing drosophila.

Drosophila suzukii Matsumura (spotted wing drosophila) has recently become a serious pest of a wide variety of fruit crops in the United States as well as in Europe, leading to substantial yearly crop losses. To enable basic and applied research of this important pest, we sequenced the D. suzukii genome to obtain a high-quality reference sequence. Here, we discuss the basic properties of the genome and transcriptome and describe patterns of genome evolution in D. suzukii and its close relatives. Our analyses and genome annotations are presented in a web portal, SpottedWingFlyBase, to facilitate public access

Complete Genome Sequences of Three Historically Important, Spatiotemporally Distinct, and Genetically Divergent Strains of Zika Virus: MR-766, P6-740, and PRVABC-59

Here, we report the 10,807-nucleotide-long consensus RNA genome sequences of three spatiotemporally distinct and genetically divergent Zika virus strains, with the functionality of their genomic sequences substantiated by reverse genetics: MR-766 (African lineage, Uganda, 1947), P6-740 (Asian lineage, Malaysia, 1966), and PRVABC-59 (Asian lineage-derived American strain, Puerto Rico, 2015)

DISC1–ATF4 transcriptional repression complex: dual regulation of the cAMP-PDE4 cascade by DISC1

Disrupted-In-Schizophrenia 1 (DISC1), a risk factor for major mental illnesses, has been studied extensively in the context of neurodevelopment. However, the role of DISC1 in neuronal signaling, particularly in conjunction with intracellular cascades that occur in response to dopamine, a neurotransmitter implicated in numerous psychiatric disorders, remains elusive. Previous data suggest that DISC1 interacts with numerous proteins that impact neuronal function, including activating transcription factor 4 (ATF4). In this study, we identify a novel DISC1 and ATF4 binding region in the genomic locus of phosphodiesterase 4D (PDE4D), a gene implicated in psychiatric disorders. We found that the loss of function of either DISC1 or ATF4 increases PDE4D9 transcription, and that the association of DISC1 with the PDE4D9 locus requires ATF4. We also show that PDE4D9 is increased by D1-type dopamine receptor dopaminergic stimulation. We demonstrate that the mechanism for this increase is due to DISC1 dissociation from the PDE4D locus in mouse brain. We further characterize the interaction of DISC1 with ATF4 to show that it is regulated via protein kinase A-mediated phosphorylation of DISC1 serine-58. Our results suggest that the release of DISC1-mediated transcriptional repression of PDE4D9 acts as feedback inhibition to regulate dopaminergic signaling. Furthermore, as DISC1 loss-of-function leads to a specific increase in PDE4D9, PDE4D9 itself may represent an attractive target for therapeutic approaches in psychiatric disorders.National Institute of General Medical Sciences (U.S.) (Award T32GM07753)National Institutes of Health (U.S.) (R01 MH091115

Integrated Conceptual Ecosystem Model Development for the Southeast Florida Coastal Marine Ecosystem

The overall goal of the MARES (MARine and Estuarine goal Setting) project for South Florida is “to reach a science-based consensus about the defining characteristics and fundamental regulating processes of a South Florida coastal marine ecosystem that is both sustainable and capable of providing the diverse ecosystem services upon which our society depends.” Through participation in a systematic process of reaching such a consensus, science can contribute more directly and effectively to the critical decisions being made both by policy makers and by natural resource and environmental management agencies. The document that follows briefly describes MARES overall and this systematic process. It then describes in considerable detail the resulting output from the first step in the process, the development of an Integrated Conceptual Ecosystem Model (ICEM) for the third subregion to be addressed by MARES, the Southeast Florida Coast (SEFC). What follows with regard to the SEFC relies upon the input received from more than 60 scientists, agency resource managers, and representatives of environmental organizations during workshops held throughout 2009–2012 in South Florida

6-Year Experience of Outpatient Total and Completion Thyroidectomy

Outpatient thyroidectomy has become slowly accepted with various published reports predominantly examining partial or subtotal thyroidectomy. Concerns regarding the safety of outpatient total and completion thyroidectomy remain, especially in regards to vocal fold paralysis, hypocalcemia, and catastrophic hematoma. We aimed to evaluate the safety of outpatient thyroid surgery in a large cohort. We conducted a retrospective review comparing outcomes in those who underwent outpatient (n=251) versus inpatient (n= 291) completion or total thyroidectomy between February 2009 and February 2015. Outpatient completion and total thyroidectomy had lower rates of temporary hypocalcemia (6% vs. 24.4%; p\u3c 0.001) and no significant difference in rates of return to emergency department (1.2% vs. 1.4%), hematoma formation (0.8% vs. 0.7%), temporary (2% vs. 4.1%) or permanent (0.4% vs. 0.7%) vocal fold paralysis, or permanent hypocalcemia (0.4% vs. 0%) compared to the inpatient group. Outpatients requiring calcium replacement had shorter duration of postoperative calcium supplementation (44.4±59.3 days vs. 63.3 ±94.4 days; p \u3c 0.001). Our data demonstrates similar safety in outpatient and inpatient total and completion thyroidectomy