Impact of motile ciliopathies on human development and clinical consequences in the newborn

Motile cilia are hairlike organelles that project outward from a tissue-restricted subset of cells to direct fluid flow. During human development motile cilia guide determination of the left-right axis in the embryo, and in the fetal and neonatal periods they have essential roles in airway clearance in the respiratory tract and regulating cerebral spinal fluid flow in the brain. Dysregulation of motile cilia is best understood through the lens of the genetic disorder primary ciliary dyskinesia (PCD). PCD encompasses all genetic motile ciliopathies resulting from over 60 known genetic mutations and has a unique but often underrecognized neonatal presentation. Neonatal respiratory distress is now known to occur in the majority of patients with PCD, laterality defects are common, and very rarely brain ventricle enlargement occurs. The developmental function of motile cilia and the effect and pathophysiology of motile ciliopathies are incompletely understood in humans. In this review, we will examine the current understanding of the role of motile cilia in human development and clinical considerations when assessing the newborn for suspected motile ciliopathies

Proteinase-activated receptor-2 modulates human macrophage differentiation andeffector function

Proteinase-activated receptor-2 (PAR-2) was shown to influence immune regulation; however, its role in human macrophage subset development and function has not been addressed. Here, PAR-2 expression and activation was investigated on granulocyte macrophage (GM)-CSF(M1) and macrophage (M)-CSF(M2) macrophages. In both macrophages, the PAR-2-activating peptide, SLIGKV, increased PAR-2 expression and regulated TNF-α and IL-10 secretion in a manner similar to LPS. In addition, HLA-DR on M1 cells also increased. Monocytes matured to an M1 phenotype in the presence of SLIGKV had reduced cell area, and released less TNF-α after LPS challenge compared with vehicle (P < 0.05, n = 3). Cells matured to an M2 phenotype with SLIGKV also had a reduced cell area and made significantly more TNF-α after LPS exposure compared to vehicle (P < 0.05, n = 3) with reduced IL-10 secretion (P < 0.05, n = 3). Thus, PAR-2 activation on macrophage subsets regulates HLA-DR and PAR-2 surface expression, and drives cytokine production. In contrast, PAR-2 activation during M1 or M2 maturation induces altered cell morphology and skewing of phenotype, as evidenced by cytokine secretion. These data suggest a complex role for PAR-2 in macrophage biology and may have implications for macrophage-driven disease in which proteinase-rich environments can influence the immune process directly

Keck/MOSFIRE Spectroscopy of z=7-8 Galaxies: Lyα\alpha Emission from a Galaxy at z=7.66

We report the results from some of the deepest Keck/Multi-Object Spectrometer For Infra-Red Exploration data yet obtained for candidate $z \gtrsim 7$ galaxies. Our data show one significant line detection with 6.5$\sigma$ significance in our combined 10 hr of integration which is independently detected on more than one night, thus ruling out the possibility that the detection is spurious. The asymmetric line profile and non-detection in the optical bands strongly imply that the detected line is Ly$\alpha$ emission from a galaxy at $z$(Ly$\alpha)=7.6637 \pm 0.0011$, making it the fourth spectroscopically confirmed galaxy via Ly$\alpha$ at $z>7.5$. This galaxy is bright in the rest-frame ultraviolet (UV; $M_{\rm UV} \sim -21.2$) with a moderately blue UV slope ($\beta=-2.2^{+0.3}_{-0.2}$), and exhibits a rest-frame Ly$\alpha$ equivalent width of EW(Ly$\alpha$) $\sim 15.6^{+5.9}_{-3.6}$ \AA. The non-detection of the 11 other $z \sim$ 7-8 galaxies in our long 10 hr integration, reaching a median 5$\sigma$ sensitivity of 28 \AA\ in the rest-frame EW(Ly$\alpha$), implies a 1.3$\sigma$ deviation from the null hypothesis of a non-evolving distribution in the rest-frame EW(Ly$\alpha$) between $3<z<6$ and $z=$ 7-8. Our results are consistent with previous studies finding a decline in Ly$\alpha$ emission at $z>6.5$, which may signal the evolving neutral fraction in the intergalactic medium at the end of the reionization epoch, although our weak evidence suggests the need for a larger statistical sample to allow for a more robust conclusion.Comment: 10 pages, 4 figures, ApJ, in pres

Reporting methodological search filter performance comparisons : a literature review

© 2014 The authors. Health Information and Libraries Journal © 2014 Health Libraries Journal.Peer reviewedPostprin

Hospice Use, Hospitalization, and Medicare Spending at the End of Life

OBJECTIVES: Prior studies associate hospice use with reduced hospitalization and spending at the end of life based on all Medicare hospice beneficiaries. In this study, we examine the impact of different lengths of hospice care and nursing home residency on hospital use and spending prior to death across 5 disease groups. METHODS: We compared inpatient hospital days and Medicare spending during the last 6 months of life using hospice versus propensity matched non-hospice beneficiaries who died in 2010, were enrolled in fee for service Medicare throughout the last 2 years of life, and were in at least 1 of 5 disease groups. Comparisons were based on length of hospice use and whether the decedent was in a nursing home during the seventh month prior to death. We regressed a categorical measure of hospice days on outcomes, controlling for observed patient characteristics. RESULTS: Hospice use over 2 weeks was associated with decreased hospital days (1-5 days overall, with greater decreases for longer hospice use) for all beneficiaries; spending was $900-$5,000 less for hospice use of 31-90 days for most beneficiaries not in nursing homes, except beneficiaries with Alzheimer's. Overall spending decreased with hospice use for beneficiaries in nursing homes with lung cancer only, with a $3,500 reduction. DISCUSSION: The Medicare hospice benefit is associated with reduced hospital care at the end of life and reduced Medicare expenditures for most enrollees. Policies that encourage timely initiation of hospice and discourage extremely short stays could increase these successes while maintaining program goals

Choosing and using methodological search filters : searchers' views

© 2014 The authors. Health Information and Libraries Journal © 2014 Health Libraries Group.Peer reviewedPostprin