Animal Models of Calcific Aortic Valve Disease

Calcific aortic valve disease (CAVD), once thought to be a degenerative disease, is now recognized to be an active pathobiological process, with chronic inflammation emerging as a predominant, and possibly driving, factor. However, many details of the pathobiological mechanisms of CAVD remain to be described, and new approaches to treat CAVD need to be identified. Animal models are emerging as vital tools to this end, facilitated by the advent of new models and improved understanding of the utility of existing models. In this paper, we summarize and critically appraise current small and large animal models of CAVD, discuss the utility of animal models for priority CAVD research areas, and provide recommendations for future animal model studies of CAVD

Northern Sourced Water dominated the Atlantic Ocean during the Last Glacial Maximum

Increased carbon sequestration in the ocean subsurface is commonly assumed to have been one of the main causes responsible for lower glacial atmospheric CO2 concentrations. Remineralized carbon must have been stored away from the atmosphere for thousands of years, yet the water mass structure accommodating such increased carbon storage continues to be debated. Here, we present new sediment-derived bottom-water neodymium isotope records that allow fingerprinting of water masses and provide a more complete picture of the Atlantic Meridional Overturning Circulation geometry during the Last Glacial Maximum. These results suggest that the vertical and meridional structure of the Atlantic water mass distribution only experienced minor changes since the last ice age. In particular, we find no compelling evidence supporting glacial southern-sourced water substantially expanding to shallower depths and farther into the Northern Hemisphere than today, which had been previously inferred from stable carbon isotope (δ13C) reconstructions. We argue that depleted δ13C values observed in the deep Northwest Atlantic do not necessarily indicate the presence of southern-sourced water. Instead, these values may represent a northern-sourced water mass with lower than modern preformed δ13C values that were further modified downstream by increased sequestration of remineralized carbon, facilitated by a more sluggish glacial deep circulation, corroborating previous evidence

Molecular Analysis of Sarcoidosis Tissues for Mycobacterium Species DNA

We performed polymerase chain reaction analysis, for Mycobacterium species 16S rRNA, rpoB, and IS6110 sequences, on 25 tissue specimens from patients with sarcoidosis and on 25 control tissue specimens consisting of mediastinal or cervical lymph nodes and lung biopsies. Mycobacterium species 16S rRNA sequences were amplified from 12 (48%) rpoB sequences from 6 (24%) of the sarcoidosis specimens. In total, 16S rRNA or rpoB sequences were amplified from 15 sarcoidosis specimens (60%) but were not detected in any of the control tissues (p=0.00002, Chi square). In three specimens, the sequences resembled Mycobacterium species other than M. tuberculosis. All specimens with sequences consistent with M. tuberculosis were negative for IS6110. We provide evidence that one of a variety of Mycobacterium species, especially organisms resembling M. tuberculosis, is found in most patients with sarcoidosis

LARES/WEBER-SAT and the equivalence principle

It has often been claimed that the proposed Earth artificial satellite LARES/WEBER-SAT-whose primary goal is, in fact, the measurement of the general relativistic Lense-Thirring effect at a some percent level-would allow to greatly improve, among (many) other things, the present-day (10^-13) level of accuracy in testing the equivalence principle as well. Recent claims point towards even two orders of magnitude better, i.e. 10^-15. In this note we show that such a goal is, in fact, unattainable by many orders of magnitude being, instead, the achievable level of the order of 10^-9.Comment: LaTex, 4 pages, no figures, no tables, 26 references. Proofs corrections included. To appear in EPL (Europhysics Letters

Factors Associated with Participation in the Oregon Summer Food Program: A Mixed Methods Analysis

The Summer Food Service Program (SFSP) was established to ensure children eligible for the National School Lunch Program (NSLP) continue to receive meals outside of the school year. However, participation in SFSP is relatively low (2.8 million annually) when compared with NSLP participation (30.4 million annually), suggesting that challenges exist in reaching children. Using a mixed methods approach, this study explored factors associated with SFSP participation. A secondary data analysis of the Oregon SFSP identified factors associated with SFSP participation at the Oregon SFSP-, sponsor-, and site-levels. Semi-structured interviews with SFSP sponsors explored barriers and facilitators to SFSP participation. Results showed increases in the total number of meals served as well as number of sponsors and sites for the Oregon SFSP over the study period. Sponsor average daily participation (ADP) demonstrated a significant decrease over the study period. Sponsors that offered more meal types, greater number of activities, and were school districts had a higher ADP. Results from interviews showed themes of organizational characteristics, site environment, and meal logistics. Findings suggest that strengthening existing sites and tailoring the current SFSP model to allow successful expansion of the program to new sites may have the greatest impact on increasing average daily participation and improve the operational sustainability of the SFSP

Characteristic Cochlear Hypoplasia in Patients with Walker-Warburg Syndrome: A Radiologic Study of the Inner Ear in alpha-Dystroglycan-Related Muscular Disorders

BACKGROUND AND PURPOSE: Walker-Warburg syndrome, muscle-eye-brain disease, and Fukuyama congenital muscular dystrophy are α-dystroglycan–related muscular disorders associated with brain malformations and eye abnormalities in which no structural inner ear abnormality has been described radiologically. We collected patients from 6 tertiary pediatric hospitals and reported the radiologic features and frequency of inner ear dysplasias. MATERIALS AND METHODS: Patients previously diagnosed clinicoradiologically with Walker-Warburg syndrome, muscle-eye-brain disease, or Fukuyama congenital muscular dystrophy were included. We recorded the pathogenic variant, when available. Brain MR imaging and/or CT findings were reviewed in consensus, and inner ear anomalies were classified according to previous description in the literature. We then correlated the clinicoradiologic phenotype with the inner ear phenotype. RESULTS: Thirteen patients fulfilled the criteria for the Walker-Warburg syndrome phenotype, 8 for muscle-eye-brain disease, and 3 for Fukuyama congenital muscular dystrophy. A dysplastic cochlea was demonstrated in 17/24. The most frequent finding was a pronounced cochlear hypoplasia type 4 with a very small anteriorly offset turn beyond the normal-appearing basal turn (12/13 patients with Walker-Warburg syndrome and 1/11 with muscle-eye-brain disease or Fukuyama congenital muscular dystophy). Two of 8 patients with muscle-eye-brain disease, 1/3 with Fukuyama congenital muscular dystrophy, and 1/13 with Walker-Warburg syndrome showed a less severe cochlear hypoplasia type 4. The remaining patients without Walker-Warburg syndrome were healthy. The vestibule and lateral semicircular canals of all patients were normal. Cranial nerve VIII was present in all patients with diagnostic MR imaging. CONCLUSIONS: Most patients with the severe α‐dystroglycanopathy Walker-Warburg syndrome phenotype have a highly characteristic cochlear hypoplasia type 4. Patients with the milder variants, muscle-eye-brain disease and Fukuyama congenital muscular dystrophy, more frequently have a normal cochlea or milder forms of hypoplasia

Migration of Zebrafish Primordial Germ Cells: A Role for Myosin Contraction and Cytoplasmic Flow

SummaryThe molecular and cellular mechanisms governing cell motility and directed migration in response to the chemokine SDF-1 are largely unknown. Here, we demonstrate that zebrafish primordial germ cells whose migration is guided by SDF-1 generate bleb-like protrusions that are powered by cytoplasmic flow. Protrusions are formed at sites of higher levels of free calcium where activation of myosin contraction occurs. Separation of the acto-myosin cortex from the plasma membrane at these sites is followed by a flow of cytoplasm into the forming bleb. We propose that polarized activation of the receptor CXCR4 leads to a rise in free calcium that in turn activates myosin contraction in the part of the cell responding to higher levels of the ligand SDF-1. The biased formation of new protrusions in a particular region of the cell in response to SDF-1 defines the leading edge and the direction of cell migration

The effect of a single-session heart rate variability biofeedback on attentional control: does stress matter?

IntroductionVagally mediated heart rate variability is an index of autonomic nervous system activity that is associated with a large variety of outcome variables including psychopathology and self-regulation. While practicing heart rate variability biofeedback over several weeks has been reliably associated with a number of positive outcomes, its acute effects are not well known. As the strongest association with vagally mediated heart rate variability has been found particularly within the attention-related subdomain of self-regulation, we investigated the acute effect of heart rate variability biofeedback on attentional control using the revised Attention Network Test.MethodsFifty-six participants were tested in two sessions. In one session each participant received a heart rate variability biofeedback intervention, and in the other session a control intervention of paced breathing at a normal ventilation rate. After the biofeedback or control intervention, participants completed the Attention Network Test using the Orienting Score as a measure of attentional control.ResultsMixed models revealed that higher resting baseline vagally mediated heart rate variability was associated with better performance in attentional control, which suggests more efficient direction of attention to target stimuli. There was no significant main effect of the intervention on attentional control. However, an interaction effect indicated better performance in attentional control after biofeedback in individuals who reported higher current stress levels.DiscussionThe results point to acute beneficial effects of heart rate variability biofeedback on cognitive performance in highly stressed individuals. Although promising, the results need to be replicated in larger or more targeted samples in order to reach stronger conclusions about the effects