Primary Cilium-Regulated EG-VEGF Signaling Facilitates Trophoblast Invasion.

PubMed

Wang, Chia-Yih; Tsai, Hui-Ling; Syu, Jhih-Siang; Chen, Ting-Yu; Su, Mei-Tsz

2017-06-01

Trophoblast invasion is an important event in embryo implantation and placental development. During these processes, endocrine gland-derived vascular endothelial growth factor (EG-VEGF) is the key regulator mediating the crosstalk at the feto-maternal interface. The primary cilium is a cellular antenna receiving environmental signals and is crucial for proper development. However, little is known regarding the role of the primary cilium in early human pregnancy. Here, we demonstrate that EG-VEGF regulates trophoblast cell invasion via primary cilia. We found that EG-VEGF activated ERK1/2 signaling and subsequent upregulation of MMP2 and MMP9, thereby facilitating cell invasion in human trophoblast HTR-8/SVneo cells. Inhibition of ERK1/2 alleviated the expression of MMPs and trophoblast cell invasion after EG-VEGF treatment. In addition, primary cilia were observed in all the trophoblast cell lines tested and, more importantly, in human first-trimester placental tissue. The receptor of EG-VEGF, PROKR1, was detected in primary cilia. Depletion of IFT88, the intraflagellar transporter required for ciliogenesis, inhibited primary cilium growth, thereby ameliorating ERK1/2 activation, MMP upregulation, and trophoblast cell invasion promoted by EG-VEGF. These findings demonstrate a novel function of primary cilia in controlling EG-VEGF-regulated trophoblast invasion and reveal the underlying molecular mechanism. J. Cell. Physiol. 232: 1467-1477, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Can Tissue Cilia Lengths and Urine Cilia Proteins Be Markers of Kidney Diseases?

PubMed

Park, Kwon Moo

2018-05-01

The primary cilium is an organelle which consists of a microtubule in the core and a surrounding cilia membrane, and has long been recognized as a "vestigial organelle". However, new evidence demonstrates that the primary cilium has a notable effect on signal transduction in the cell and is associated with some genetic and non-genetic diseases. In the kidney, the primary cilium protrudes into the Bowman's space and the tubular lumen from the apical side of epithelial cells. The length of primary cilia is dynamically altered during the normal cell cycle, being shortened by retraction into the cell body at the entry of cell division and elongated at differentiation. Furthermore, the length of primary cilia is also dynamically changed in the cells, as a result and/or cause, during the progression of various kidney diseases including acute kidney injury and chronic kidney disease. Notably, recent data has demonstrated that the shortening of the primary cilium in the cell is associated with fragmentation, apart from retraction into the cell body, in the progression of diseases and that the fragmented primary cilia are released into the urine. This data reveals that the alteration of primary cilia length could be related to the progression of diseases. This review will consider if primary cilia length alteration is associated with the progression of kidney diseases and if the length of tissue primary cilia and the presence or increase of cilia proteins in the urine is indicative of kidney diseases.

The role of the cilium in hereditary tumor predisposition syndromes

PubMed Central

Klasson, Timothy D.; Giles, Rachel H.

2014-01-01

The primary cilium is a highly conserved cell organelle that is closely connected to processes involved in cell patterning and replication. Amongst their many functions, cilia act as “signal towers” through which cell-cell signaling cascades pass. Dysfunction of cilia or the myriad processes that are connected with cilium function can lead to disease. Due to the sheer number of cellular processes that at some point involve the primary cilium, the effects of misregulation are highly heterogeneous between different cell populations. However, because of the importance of primary cilia in the development, growth, patterning and orientation of cells and tissues, a common thread has emerged in which defective cilia can lead to disorganization, which can contribute to the growth of neoplasms, including cancer and pre-cancerous phenotypes. Because cilia are so vital for signaling during cell replication and the cell fate decisions that are important in childhood growth, symptoms often arise early in life. Here we review recent work connecting misregulation of the primary cilium with tumor formation in a variety of tissues in the developing body, with a particular focus on the syndromes in which classic tumor genes are mutated, including von Hippel-Lindau disease (OMIM 193300), adenomatous polyposis coli (OMIM 175100), tuberous sclerosis (OMIM 191100) and Birt-Hogg-Dubé syndrome (OMIM 135150). Timely diagnosis of these syndromes is essential for entry into appropriate screening protocols, which have been shown to effectively prolong life expectancy in these cohorts of patients. PMID:27625869

N-terminal dual lipidation-coupled molecular targeting into the primary cilium.

PubMed

Kumeta, Masahiro; Panina, Yulia; Yamazaki, Hiroya; Takeyasu, Kunio; Yoshimura, Shige H

2018-06-13

The primary cilium functions as an "antenna" for cell signaling, studded with characteristic transmembrane receptors and soluble protein factors, raised above the cell surface. In contrast to the transmembrane proteins, targeting mechanisms of nontransmembrane ciliary proteins are poorly understood. We focused on a pathogenic mutation that abolishes ciliary localization of retinitis pigmentosa 2 protein and revealed a dual acylation-dependent ciliary targeting pathway. Short N-terminal sequences which contain myristoylation and palmitoylation sites are sufficient to target a marker protein into the cilium in a palmitoylation-dependent manner. A Golgi-localized palmitoyltransferase DHHC-21 was identified as the key enzyme controlling this targeting pathway. Rapid turnover of the targeted protein was ensured by cholesterol-dependent membrane fluidity, which balances highly and less-mobile populations of the molecules within the cilium. This targeting signal was found in a set of signal transduction molecules, suggesting a general role of this pathway in proper ciliary organization, and dysfunction in ciliary disorders. © 2018 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

Human basal body basics.

PubMed

Vertii, Anastassiia; Hung, Hui-Fang; Hehnly, Heidi; Doxsey, Stephen

2016-01-01

In human cells, the basal body (BB) core comprises a ninefold microtubule-triplet cylindrical structure. Distal and subdistal appendages are located at the distal end of BB, where they play indispensable roles in cilium formation and function. Most cells that arrest in the G0 stage of the cell cycle initiate BB docking at the plasma membrane followed by BB-mediated growth of a solitary primary cilium, a structure required for sensing the extracellular environment and cell signaling. In addition to the primary cilium, motile cilia are present in specialized cells, such as sperm and airway epithelium. Mutations that affect BB function result in cilia dysfunction. This can generate syndromic disorders, collectively called ciliopathies, for which there are no effective treatments. In this review, we focus on the features and functions of BBs and centrosomes in Homo sapiens.

Maintaining protein composition in cilia.

PubMed

Stephen, Louise A; Elmaghloob, Yasmin; Ismail, Shehab

2017-12-20

The primary cilium is a sensory organelle that is vital in regulating several signalling pathways. Unlike most organelles cilia are open to the rest of the cell, not enclosed by membranes. The distinct protein composition is crucial to the function of cilia and many signalling proteins and receptors are specifically concentrated within distinct compartments. To maintain this composition, a mechanism is required to deliver proteins to the cilium whilst another must counter the entropic tendency of proteins to distribute throughout the cell. The combination of the two mechanisms should result in the concentration of ciliary proteins to the cilium. In this review we will look at different cellular mechanisms that play a role in maintaining the distinct composition of cilia, including regulation of ciliary access and trafficking of ciliary proteins to, from and within the cilium.

Vulnerability of Normal Human Mammary Epithelial Cells to Oncogenic Transformation

DTIC Science & Technology

2012-04-01

Hatzimasoura, E, Garbe, JC, Stampfer, MR, Koh, J, Beach, DH (2010). Primary cilium dependent and independent Hedgehog signaling inhibits p16INK4A. Mol...e8697 Molecular Cell ArticlePrimary Cilium-Dependent and -Independent Hedgehog Signaling Inhibits p16INK4A Cleo L. Bishop,1,* Ann-Marie H. Bergin,1,4...genome-wide siRNA analysis of p16INK4a (p16) modulators, we identify the Hedgehog (Hh) pathway component SUFU and formally demonstrate that Hh signaling

Toolkit for the Automated Characterization of Optical Trapping Forces on Microscopic Particles

NASA Astrophysics Data System (ADS)

Glaser, Joseph; Hoeprich, David; Resnick, Andrew

2014-03-01

Optical traps have been in use in microbiological studies for the past 40 years to obtain noninvasive control of microscopic particles. However, the magnitude of the applied forces is often unknown. Therefore, we have developed an automated data acquisition and processing system which characterizes trap properties for known particle geometries. Extensive experiments and measurements utilizing well-characterized objects were performed and compared to literature to confirm the system's performance. This system will enable the future analysis of a trapped primary cilium, a slender rod-shaped organelle with aspect ratio L/R >30, where `L' is the cilium length and `R' the cilium diameter. The trapping of cilia is of primary importance, as it will lead to the precise measurements of mechanical properties of the organelle and its significance to the epithelial cell. Support from the National Institutes of Health, 1R15DK092716 is gratefully acknowledged.

Mechanosensation and the Primary Cilium

NASA Astrophysics Data System (ADS)

Glaser, Joseph; Resnick, Andrew

2010-10-01

The primary cilium has come under increased scrutiny as a site for mechano- and chemosensation by cells. We have undertaken a program of study using mouse renal cell lines from the cortical collecting duct to quantify how mechanical forces arising from fluid shear are transduced into cellular responses. Fluid flow through a model nephron has been analyzed to determine the in vivo forces. A novel tissue culture flow chamber permitting accurate reproduction of physiologically relevant conditions has been calibrated. We have determined that in vivo conditions can be accurately modeled in our flow chamber.

The ciliopathy gene Rpgrip1l is essential for hair follicle development.

PubMed

Chen, Jiang; Laclef, Christine; Moncayo, Alejandra; Snedecor, Elizabeth R; Yang, Ning; Li, Li; Takemaru, Ken-Ichi; Paus, Ralf; Schneider-Maunoury, Sylvie; Clark, Richard A

2015-03-01

The primary cilium is essential for skin morphogenesis through regulating the Notch, Wnt, and hedgehog signaling pathways. Prior studies on the functions of primary cilia in the skin were based on the investigations of genes that are essential for cilium formation. However, none of these ciliogenic genes has been linked to ciliopathy, a group of disorders caused by abnormal formation or function of cilia. To determine whether there is a genetic and molecular link between ciliopathies and skin morphogenesis, we investigated the role of RPGRIP1L, a gene mutated in Joubert (JBTS) and Meckel (MKS) syndromes, two severe forms of ciliopathy, in the context of skin development. We found that RPGRIP1L is essential for hair follicle morphogenesis. Specifically, disrupting the Rpgrip1l gene in mice resulted in reduced proliferation and differentiation of follicular keratinocytes, leading to hair follicle developmental defects. These defects were associated with significantly decreased primary cilium formation and attenuated hedgehog signaling. In contrast, we found that hair follicle induction and polarization and the development of interfollicular epidermis were unaffected. This study indicates that RPGRIP1L, a ciliopathy gene, is essential for hair follicle morphogenesis likely through regulating primary cilia formation and the hedgehog signaling pathway.

Non-essential role for cilia in coordinating precise alignment of lens fibres

PubMed Central

Sugiyama, Yuki; Shelley, Elizabeth J.; Yoder, Bradley K.; Kozmik, Zbynek; May-Simera, Helen L.; Beales, Philip L.; Lovicu, Frank J.; McAvoy, John W.

2016-01-01

The primary cilium, a microtubule-based organelle found in most cells, is a centre for mechano-sensing fluid movement and cellular signalling, notably through the Hedgehog pathway. We recently found that each lens fibre cell has an apically situated primary cilium that is polarised to the side of the cell facing the anterior pole of the lens. The direction of polarity is similar in neighbouring cells so that in the global view, lens fibres exhibit planar cell polarity (PCP) along the equatorial-anterior polar axis. Ciliogenesis has been associated with the establishment of PCP, although the exact relationship between PCP and the role of cilia is still controversial. To test the hypothesis that the primary cilia have a role in coordinating the precise alignment/orientation of the fibre cells, IFT88, a key component of the intraflagellar transport (IFT) complex, was removed specifically from the lens at different developmental stages using several lens-specific Cre-expressing mouse lines (MLR10- and LR-Cre). Irrespective of which Cre-line was adopted, both demonstrated that in IFT88-depleted cells, the ciliary axoneme was absent or substantially shortened, confirming the disruption of primary cilia formation. However no obvious histological defects were detected even when IFT88 was removed from the lens placode as early as E9.5. Specifically, the lens fibres aligned/oriented towards the poles to form the characteristic Y-shaped sutures as normal. Consistent with this, in primary lens epithelial explants prepared from these conditional knockout mouse lenses, the basal bodies still showed polarised localisation at the apical surface of elongating cells upon FGF-induced fibre differentiation. We further investigated the lens phenotype in knockouts of Bardet–Biedl Syndrome (BBS) proteins 4 and 8, the components of the BBSome complex which modulate ciliary function. In these BBS4 and 8 knockout lenses, again we found the pattern of the anterior sutures formed by the apical tips of elongating/migrating fibres were comparable to the control lenses. Taken together, these results indicate that primary cilia do not play an essential role in the precise cellular alignment/orientation of fibre cells. Thus, it appears that in the lens cilia are not required to establish PCP. PMID:26825015

The role of Rpgrip1l, a component of the primary cilium, in adipocyte development and function.

PubMed

Carli, Jayne F Martin; LeDuc, Charles A; Zhang, Yiying; Stratigopoulos, George; Leibel, Rudolph L

2018-02-21

Genetic variants within the FTO (α-ketoglutarate-dependent dioxygenase) gene have been strongly associated with a modest increase in adiposity as a result of increased food intake. These risk alleles are associated with decreased expression of both FTO and neighboring RPGRIP1L (retinitis pigmentosa GTPase regulator-interacting protein 1 like). RPGRIP1L encodes a protein that is critical to the function of the primary cilium, which conveys extracellular information to the cell. Rpgrip1l +/- mice exhibit increased adiposity, in part, as a result of hyperphagia. Here, we describe the effects of Rpgrip1l in adipocytes that may contribute to the adiposity phenotype observed in these animals and possibly in humans who segregate for FTO risk alleles. Loss of Rpgrip1l in 3T3-L1 preadipocytes increased the number of cells that are capable of differentiating into mature adipocytes. Knockout of Rpgrip1l in mature adipocytes using Adipoq-Cre did not increase adiposity in mice that were fed chow or a high-fat diet. We also did not observe any effects of Rpgrip1l knockdown in mature 3T3-L1 adipocytes. Thus, to the extent that Rpgrip1l affects cell-autonomous adipose tissue function, it may do so as a result of the effects conveyed in preadipocytes in which the primary cilium is functionally important. We propose that decreased RPGRIP1L expression in preadipocytes in humans who segregate for FTO obesity risk alleles may increase the storage capacity of adipose tissue.-Martin Carli, J. F., LeDuc, C. A., Zhang, Y., Stratigopoulos, G., Leibel, R. L. The role of Rpgrip1l, a component of the primary cilium, in adipocyte development and function.

Primary Cilia Modulate IHH Signal Transduction in Response to Hydrostatic Loading of Growth Plate Chondrocytes

PubMed Central

Shao, Y, Yvonne Y.; Wang, Lai; Welter, J, Jean F.; Ballock, R. Tracy

2011-01-01

Indian Hedgehog (Ihh) is a key component of the regulatory apparatus governing chondrocyte proliferation and differentiation in the growth plate. Recent studies have demonstrated that the primary cilium is the site of Ihh signaling within the cell, and that primary cilia are essential for bone and cartilage formation. Primary cilia are also postulated to act as mechanosensory organelles that transduce mechanical forces acting on the cell into biological signals. In this study, we used a hydrostatic compression system to examine Ihh signal transduction under the influence of mechanical load. Our results demonstrate that hydrostatic compression increased both Ihh gene expression and Ihh-responsive Gli-luciferase activity. These increases were aborted by disrupting the primary cilia structure with chloral hydrate. These results suggest that growth plate chondrocytes respond to hydrostatic loading by increasing Ihh signaling, and that the primary cilium is required for this mechano-biological signal transduction to occur. PMID:21930256

Regulation of Cilium Length and Intraflagellar Transport by the RCK-Kinases ICK and MOK in Renal Epithelial Cells

PubMed Central

Broekhuis, Joost R.; Verhey, Kristen J.; Jansen, Gert

2014-01-01

Primary cilia are important sensory organelles. They exist in a wide variety of lengths, which could reflect different cell-specific functions. How cilium length is regulated is unclear, but it probably involves intraflagellar transport (IFT), which transports protein complexes along the ciliary axoneme. Studies in various organisms have identified the small, conserved family of ros-cross hybridizing kinases (RCK) as regulators of cilium length. Here we show that Intestinal Cell Kinase (ICK) and MAPK/MAK/MRK overlapping kinase (MOK), two members of this family, localize to cilia of mouse renal epithelial (IMCD-3) cells and negatively regulate cilium length. To analyze the effects of ICK and MOK on the IFT machinery, we set up live imaging of five fluorescently tagged IFT proteins: KIF3B, a subunit of kinesin-II, the main anterograde IFT motor, complex A protein IFT43, complex B protein IFT20, BBSome protein BBS8 and homodimeric kinesin KIF17, whose function in mammalian cilia is unclear. Interestingly, all five proteins moved at ∼0.45 µm/s in anterograde and retrograde direction, suggesting they are all transported by the same machinery. Moreover, GFP tagged ICK and MOK moved at similar velocities as the IFT proteins, suggesting they are part of, or transported by the IFT machinery. Indeed, loss- or gain-of-function of ICK affected IFT speeds: knockdown increased anterograde velocities, whereas overexpression reduced retrograde speed. In contrast, MOK knockdown or overexpression did not affect IFT speeds. Finally, we found that the effects of ICK or MOK knockdown on cilium length and IFT are suppressed by rapamycin treatment, suggesting that these effects require the mTORC1 pathway. Our results confirm the importance of RCK kinases as regulators of cilium length and IFT. However, whereas some of our results suggest a direct correlation between cilium length and IFT speed, other results indicate that cilium length can be modulated independent of IFT speed. PMID:25243405

An Experimental and Computational Analysis of Primary Cilia Deflection Under Fluid Flow

PubMed Central

Downs, Matthew E.; Nguyen, An M.; Herzog, Florian A.; Hoey, David A.; Jacobs, Christopher R.

2013-01-01

In this work we have developed a novel model of the deflection of primary cilia experiencing fluid flow accounting for phenomena not previously considered. Specifically, we developed a large rotation formulation that accounts for rotation at the base of the cilium, the initial shape of the cilium and fluid drag at high deflection angles. We utilized this model to analyze full three dimensional datasets of primary cilia deflecting under fluid flow acquired with high-speed confocal microscopy. We found a wide variety of previously unreported bending shapes and behaviors. We also analyzed post-flow relaxation patterns. Results from our combined experimental and theoretical approach suggest that the average flexural rigidity of primary cilia might be higher than previously reported (Schwartz et al. 1997). In addition our findings indicate the mechanics of primary cilia are richly varied and mechanisms may exist to alter their mechanical behavior. PMID:22452422

Asynchronous beating of cilia enhances particle capture rate

NASA Astrophysics Data System (ADS)

Ding, Yang; Kanso, Eva

2014-11-01

Many aquatic micro-organisms use beating cilia to generate feeding currents and capture particles in surrounding fluids. One of the capture strategies is to ``catch up'' with particles when a cilium is beating towards the overall flow direction (effective stroke) and intercept particles on the downstream side of the cilium. Here, we developed a 3D computational model of a cilia band with prescribed motion in a viscous fluid and calculated the trajectories of the particles with different sizes in the fluid. We found an optimal particle diameter that maximizes the capture rate. The flow field and particle motion indicate that the low capture rate of smaller particles is due to the laminar flow in the neighbor of the cilia, whereas larger particles have to move above the cilia tips to get advected downstream which decreases their capture rate. We then analyzed the effect of beating coordination between neighboring cilia on the capture rate. Interestingly, we found that asynchrony of the beating of the cilia can enhance the relative motion between a cilium and the particles near it and hence increase the capture rate.

An siRNA-based functional genomics screen for the identification of regulators of ciliogenesis and ciliopathy genes

PubMed Central

Racher, Hilary; Phelps, Ian G.; Toedt, Grischa; Kennedy, Julie; Wunderlich, Kirsten A.; Sorusch, Nasrin; Abdelhamed, Zakia A.; Natarajan, Subaashini; Herridge, Warren; van Reeuwijk, Jeroen; Horn, Nicola; Boldt, Karsten; Parry, David A.; Letteboer, Stef J.F.; Roosing, Susanne; Adams, Matthew; Bell, Sandra M.; Bond, Jacquelyn; Higgins, Julie; Morrison, Ewan E.; Tomlinson, Darren C.; Slaats, Gisela G.; van Dam, Teunis J. P.; Huang, Lijia; Kessler, Kristin; Giessl, Andreas; Logan, Clare V.; Boyle, Evan A.; Shendure, Jay; Anazi, Shamsa; Aldahmesh, Mohammed; Al Hazzaa, Selwa; Hegele, Robert A.; Ober, Carole; Frosk, Patrick; Mhanni, Aizeddin A.; Chodirker, Bernard N.; Chudley, Albert E.; Lamont, Ryan; Bernier, Francois P.; Beaulieu, Chandree L.; Gordon, Paul; Pon, Richard T.; Donahue, Clem; Barkovich, A. James; Wolf, Louis; Toomes, Carmel; Thiel, Christian T.; Boycott, Kym M.; McKibbin, Martin; Inglehearn, Chris F.; Stewart, Fiona; Omran, Heymut; Huynen, Martijn A.; Sergouniotis, Panagiotis I.; Alkuraya, Fowzan S.; Parboosingh, Jillian S.; Innes, A Micheil; Willoughby, Colin E.; Giles, Rachel H.; Webster, Andrew R.; Ueffing, Marius; Blacque, Oliver; Gleeson, Joseph G.; Wolfrum, Uwe; Beales, Philip L.; Gibson, Toby

2015-01-01

Defects in primary cilium biogenesis underlie the ciliopathies, a growing group of genetic disorders. We describe a whole genome siRNA-based reverse genetics screen for defects in biogenesis and/or maintenance of the primary cilium, obtaining a global resource. We identify 112 candidate ciliogenesis and ciliopathy genes, including 44 components of the ubiquitin-proteasome system, 12 G-protein-coupled receptors, and three pre-mRNA processing factors (PRPF6, PRPF8 and PRPF31) mutated in autosomal dominant retinitis pigmentosa. The PRPFs localise to the connecting cilium, and PRPF8- and PRPF31-mutated cells have ciliary defects. Combining the screen with exome sequencing data identified recessive mutations in PIBF1/CEP90 and C21orf2/LRRC76 as causes of the ciliopathies Joubert and Jeune syndromes. Biochemical approaches place C21orf2 within key ciliopathy-associated protein modules, offering an explanation for the skeletal and retinal involvement observed in individuals with C21orf2-variants. Our global, unbiased approaches provide insights into ciliogenesis complexity and identify roles for unanticipated pathways in human genetic disease. PMID:26167768

Intraflagellar transport protein 122 antagonizes Sonic Hedgehog signaling and controls ciliary localization of pathway components.

PubMed

Qin, Jian; Lin, Yulian; Norman, Ryan X; Ko, Hyuk W; Eggenschwiler, Jonathan T

2011-01-25

Primary cilia are required for proper Sonic Hedgehog (Shh) signaling in mammals. However, their role in the signal transduction process remains unclear. We have identified sister of open brain (sopb), a null allele of mouse Intraflagellar transport protein 122 (Ift122). IFT122 negatively regulates the Shh pathway in the cilium at a step downstream of the Shh ligand and the transmembrane protein Smoothened, but upstream of the Gli2 transcription factor. Ift122(sopb) mutants generate primary cilia, but they show features of defective retrograde intraflagellar transport. IFT122 controls the ciliary localization of Shh pathway regulators in different ways. Disruption of IFT122 leads to accumulation of Gli2 and Gli3 at cilia tips while blocking the ciliary localization of the antagonist TULP3. Suppressor of Fused and Smoothened localize to the cilium through an IFT122-independent mechanism. We propose that the balance between positive and negative regulators of the Shh pathway at the cilium tip controls the output of the pathway and that Shh signaling regulates this balance through intraflagellar transport.

Primary cilia proteins: ciliary and extraciliary sites and functions.

PubMed

Hua, Kiet; Ferland, Russell J

2018-05-01

Primary cilia are immotile organelles known for their roles in development and cell signaling. Defects in primary cilia result in a range of disorders named ciliopathies. Because this organelle can be found singularly on almost all cell types, its importance extends to most organ systems. As such, elucidating the importance of the primary cilium has attracted researchers from all biological disciplines. As the primary cilia field expands, caution is warranted in attributing biological defects solely to the function of this organelle, since many of these "ciliary" proteins are found at other sites in cells and likely have non-ciliary functions. Indeed, many, if not all, cilia proteins have locations and functions outside the primary cilium. Extraciliary functions are known to include cell cycle regulation, cytoskeletal regulation, and trafficking. Cilia proteins have been observed in the nucleus, at the Golgi apparatus, and even in immune synapses of T cells (interestingly, a non-ciliated cell). Given the abundance of extraciliary sites and functions, it can be difficult to definitively attribute an observed phenotype solely to defective cilia rather than to some defective extraciliary function or a combination of both. Thus, extraciliary sites and functions of cilia proteins need to be considered, as well as experimentally determined. Through such consideration, we will understand the true role of the primary cilium in disease as compared to other cellular processes' influences in mediating disease (or through a combination of both). Here, we review a compilation of known extraciliary sites and functions of "cilia" proteins as a means to demonstrate the potential non-ciliary roles for these proteins.

Primary cilia modulate Ihh signal transduction in response to hydrostatic loading of growth plate chondrocytes.

PubMed

Shao, Yvonne Y; Wang, Lai; Welter, Jean F; Ballock, R Tracy

2012-01-01

Indian hedgehog (Ihh) is a key component of the regulatory apparatus governing chondrocyte proliferation and differentiation in the growth plate. Recent studies have demonstrated that the primary cilium is the site of Ihh signaling within the cell, and that primary cilia are essential for bone and cartilage formation. Primary cilia are also postulated to act as mechanosensory organelles that transduce mechanical forces acting on the cell into biological signals. In this study, we used a hydrostatic compression system to examine Ihh signal transduction under the influence of mechanical load. Our results demonstrate that hydrostatic compression increased both Ihh gene expression and Ihh-responsive Gli-luciferase activity. These increases were aborted by disrupting the primary cilia structure with chloral hydrate. These results suggest that growth plate chondrocytes respond to hydrostatic loading by increasing Ihh signaling, and that the primary cilium is required for this mechano-biological signal transduction to occur. Copyright © 2011 Elsevier Inc. All rights reserved.

The periciliary ring in polarized epithelial cells is a hot spot for delivery of the apical protein gp135

PubMed Central

Stoops, Emily H.; Hull, Michael; Olesen, Christina; Mistry, Kavita; Harder, Jennifer L.; Rivera-Molina, Felix; Toomre, Derek

2015-01-01

In polarized epithelial cells, newly synthesized cell surface proteins travel in carrier vesicles from the trans Golgi network to the apical or basolateral plasma membrane. Despite extensive research on polarized trafficking, the sites of protein delivery are not fully characterized. Here we use the SNAP tag system to examine the site of delivery of the apical glycoprotein gp135. We show that a cohort of gp135 is delivered to a ring surrounding the base of the primary cilium, followed by microtubule-dependent radial movement away from the cilium. Delivery to the periciliary ring was specific to newly synthesized and not recycling protein. A subset of this newly delivered protein traverses the basolateral membrane en route to the apical membrane. Crumbs3a, another apical protein, was not delivered to the periciliary region, instead making its initial apical appearance in a pattern that resembled its steady-state distribution. Our results demonstrate a surprising “hot spot” for gp135 protein delivery at the base of the primary cilium and suggest the existence of a novel microtubule-based directed movement of a subset of apical surface proteins. PMID:26504168

Dynamic remodeling of membrane composition drives cell cycle through primary cilia excision

PubMed Central

Phua, Siew Cheng; Chiba, Shuhei; Suzuki, Masako; Su, Emily; Roberson, Elle C.; Pusapati, Ganesh V.; Setou, Mitsutoshi; Rohatgi, Rajat; Reiter, Jeremy F.; Ikegami, Koji; Inoue, Takanari

2017-01-01

The life cycle of a primary cilium begins in quiescence and ends prior to mitosis. In quiescent cells, primary cilium insulates itself from contiguous dynamic membrane processes on the cell surface to function as a stable signaling apparatus. Here, we demonstrate that basal restriction of ciliary structure dynamics is established by cilia-enriched phosphoinositide 5-phosphatase, Inpp5e. Growth induction displaces ciliary Inpp5e and accumulates phosphatidylinositol 4,5-bisphosphate to distal cilia. This triggers otherwise forbidden actin polymerization in primary cilia, which excises cilia tips in a process we call cilia decapitation. Whilst cilia disassembly is traditionally thought to occur solely through resorption, we show that an acute loss of IFT-B through cilia decapitation precedes resorption. Finally, we propose that cilia decapitation induces mitogenic signaling and constitutes a molecular link between the cilia life cycle and cell-division cycle. This newly defined ciliary mechanism may find significance in cell proliferation control during normal development and cancer. PMID:28086093

Hsp90α forms a stable complex at the cilium neck for the interaction of signalling molecules in IGF-1 receptor signalling.

PubMed

Wang, Hongzhong; Zou, Xinle; Wei, Zhuang; Wu, Yuan; Li, Rongxia; Zeng, Rong; Chen, Zhengjun; Liao, Kan

2015-01-01

The primary cilium is composed of an axoneme that protrudes from the cell surface, a basal body beneath the membrane and a transition neck in between. It is a sensory organelle on the plasma membrane, involved in mediating extracellular signals. In the transition neck region of the cilium, the microtubules change from triplet to doublet microtubules. This region also contains the transition fibres that crosslink the axoneme with the membrane and the necklace proteins that regulate molecules being transported into and out of the cilium. In this protein-enriched, complex area it is important to maintain the correct assembly of all of these proteins. Here, through immunofluorescent staining and protein isolation, we identify the molecular chaperone Hsp90α clustered at the periciliary base. At the transition neck region, phosphorylated Hsp90α forms a stable ring around the axoneme. Heat shock treatment causes Hsp90α to dissipate and induces resorption of cilia. We further identify that Hsp90α at the transition neck region represents a signalling platform on which IRS-1 interacts with intracellular downstream signalling molecules involved in IGF-1 receptor signalling. © 2015. Published by The Company of Biologists Ltd.

Primary Cilia Negatively Regulate Melanogenesis in Melanocytes and Pigmentation in a Human Skin Model.

PubMed

Choi, Hyunjung; Shin, Ji Hyun; Kim, Eun Sung; Park, So Jung; Bae, Il-Hong; Jo, Yoon Kyung; Jeong, In Young; Kim, Hyoung-June; Lee, Youngjin; Park, Hea Chul; Jeon, Hong Bae; Kim, Ki Woo; Lee, Tae Ryong; Cho, Dong-Hyung

2016-01-01

The primary cilium is an organelle protruding from the cell body that senses external stimuli including chemical, mechanical, light, osmotic, fluid flow, and gravitational signals. Skin is always exposed to the external environment and responds to external stimuli. Therefore, it is possible that primary cilia have an important role in skin. Ciliogenesis was reported to be involved in developmental processes in skin, such as keratinocyte differentiation and hair formation. However, the relation between skin pigmentation and primary cilia is largely unknown. Here, we observed that increased melanogenesis in melanocytes treated with a melanogenic inducer was inhibited by a ciliogenesis inducer, cytochalasin D, and serum-free culture. However, these inhibitory effects disappeared in GLI2 knockdown cells. In addition, activation of sonic hedgehog (SHH)-smoothened (Smo) signaling pathway by a Smo agonist, SAG inhibited melanin synthesis in melanocytes and pigmentation in a human skin model. On the contrary, an inhibitor of primary cilium formation, ciliobrevin A1, activated melanogenesis in melanocytes. These results suggest that skin pigmentation may be regulated partly by the induction of ciliogenesis through Smo-GLI2 signaling.

Mechanical Properties of Primary Cilia

NASA Astrophysics Data System (ADS)

Battle, Christopher; Schmidt, Christoph F.

2013-03-01

Recent studies have shown that the primary cilium, long thought to be a vestigial cellular appendage with no function, is involved in a multitude of sensory functions. One example, interesting from both a biophysical and medical standpoint, is the primary cilium of kidney epithelial cells, which acts as a mechanosensitive flow sensor. Genetic defects in ciliary function can cause, e.g., polycystic kidney disease (PKD). The material properties of these non-motile, microtubule-based 9 +0 cilia, and the way they are anchored to the cell cytoskeleton, are important to know if one wants to understand the mechano-electrochemical response of these cells, which is mediated by their cilia. We have probed the mechanical properties, boundary conditions, and dynamics of the cilia of MDCK cells using optical traps and DIC/fluorescence microscopy. We found evidence for both elastic relaxation of the cilia themselves after bending and for compliance in the intracellular anchoring structures. Angular and positional fluctuations of the cilia reflect both thermal excitations and cellular driving forces.

Sonic Hedgehog promotes proliferation of Notch-dependent monociliated choroid plexus tumour cells

PubMed Central

Li, Li; Grausam, Katie B.; Wang, Jun; Lun, Melody P.; Ohli, Jasmin; Lidov, Hart G. W.; Calicchio, Monica L.; Zeng, Erliang; Salisbury, Jeffrey L.; Wechsler-Reya, Robert J.; Lehtinen, Maria K.; Schüller, Ulrich; Zhao, Haotian

2016-01-01

Aberrant Notch signaling has been linked to many cancers including choroid plexus (CP) tumours, a group of rare and predominantly pediatric brain neoplasms. We developed animal models of CP tumours by inducing sustained expression of Notch1 that recapitulate properties of human CP tumours with aberrant NOTCH signaling. Whole transcriptome and functional analyses showed that tumour cell proliferation is associated with Sonic Hedgehog (Shh) in the tumour microenvironment. Unlike CP epithelial cells, which have multiple primary cilia, tumour cells possess a solitary primary cilium as a result of Notch-mediated suppression of multiciliate diffferentiation. A Shh-driven signaling cascade in the primary cilium occurs in tumour cells but not in epithelial cells. Lineage studies show that CP tumours arise from mono-ciliated progenitors in the roof plate characterized by elevated Notch signaling. Abnormal SHH signaling and distinct ciliogenesis are detected in human CP tumours, suggesting SHH pathway and cilia differentiation as potential therapeutic avenues. PMID:26999738

C-NAP1 and rootletin restrain DNA damage-induced centriole splitting and facilitate ciliogenesis.

PubMed

Conroy, Pauline C; Saladino, Chiara; Dantas, Tiago J; Lalor, Pierce; Dockery, Peter; Morrison, Ciaran G

2012-10-15

Cilia are found on most human cells and exist as motile cilia or non-motile primary cilia. Primary cilia play sensory roles in transducing various extracellular signals, and defective ciliary functions are involved in a wide range of human diseases. Centrosomes are the principal microtubule-organizing centers of animal cells and contain two centrioles. We observed that DNA damage causes centriole splitting in non-transformed human cells, with isolated centrioles carrying the mother centriole markers CEP170 and ninein but not kizuna or cenexin. Loss of centriole cohesion through siRNA depletion of C-NAP1 or rootletin increased radiation-induced centriole splitting, with C-NAP1-depleted isolated centrioles losing mother markers. As the mother centriole forms the basal body in primary cilia, we tested whether centriole splitting affected ciliogenesis. While irradiated cells formed apparently normal primary cilia, most cilia arose from centriolar clusters, not from isolated centrioles. Furthermore, C-NAP1 or rootletin knockdown reduced primary cilium formation. Therefore, the centriole cohesion apparatus at the proximal end of centrioles may provide a target that can affect primary cilium formation as part of the DNA damage response.

Mutations in CSPP1 lead to classical Joubert syndrome.

PubMed

Akizu, Naiara; Silhavy, Jennifer L; Rosti, Rasim Ozgur; Scott, Eric; Fenstermaker, Ali G; Schroth, Jana; Zaki, Maha S; Sanchez, Henry; Gupta, Neerja; Kabra, Madhulika; Kara, Majdi; Ben-Omran, Tawfeg; Rosti, Basak; Guemez-Gamboa, Alicia; Spencer, Emily; Pan, Roger; Cai, Na; Abdellateef, Mostafa; Gabriel, Stacey; Halbritter, Jan; Hildebrandt, Friedhelm; van Bokhoven, Hans; Gunel, Murat; Gleeson, Joseph G

2014-01-02

Joubert syndrome and related disorders (JSRDs) are genetically heterogeneous and characterized by a distinctive mid-hindbrain malformation. Causative mutations lead to primary cilia dysfunction, which often results in variable involvement of other organs such as the liver, retina, and kidney. We identified predicted null mutations in CSPP1 in six individuals affected by classical JSRDs. CSPP1 encodes a protein localized to centrosomes and spindle poles, as well as to the primary cilium. Despite the known interaction between CSPP1 and nephronophthisis-associated proteins, none of the affected individuals in our cohort presented with kidney disease, and further, screening of a large cohort of individuals with nephronophthisis demonstrated no mutations. CSPP1 is broadly expressed in neural tissue, and its encoded protein localizes to the primary cilium in an in vitro model of human neurogenesis. Here, we show abrogated protein levels and ciliogenesis in affected fibroblasts. Our data thus suggest that CSPP1 is involved in neural-specific functions of primary cilia. Copyright © 2014 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Ultrastructural characterization of primary cilia in pathologically characterized human glioblastoma multiforme (GBM) tumors.

PubMed

Moser, Joanna J; Fritzler, Marvin J; Rattner, Jerome B

2014-01-01

Primary cilia are non-motile sensory cytoplasmic organelles that are involved in cell cycle progression. Ultrastructurally, the primary cilium region is complex, with normal ciliogenesis progressing through five distinct morphological stages in human astrocytes. Defects in early stages of ciliogenesis are key features of astrocytoma/glioblastoma cell lines and provided the impetus for the current study which describes the morphology of primary cilia in molecularly characterized human glioblastoma multiforme (GBM) tumors. Seven surgically resected human GBM tissue samples were molecularly characterized according to IDH1/2 mutation status, EGFR amplification status and MGMT promoter methylation status and were examined for primary cilia expression and structure using indirect immunofluorescence and electron microscopy. We report for the first time that primary cilia are disrupted in the early stages of ciliogenesis in human GBM tumors. We confirm that immature primary cilia and basal bodies/centrioles have aberrant ciliogenesis characteristics including absent paired vesicles, misshaped/swollen vesicular hats, abnormal configuration of distal appendages, and discontinuity of centriole microtubular blades. Additionally, the transition zone plate is able to form in the absence of paired vesicles on the distal end of the basal body and when a cilium progresses beyond the early stages of ciliogenesis, it has electron dense material clumped along the transition zone and a darkening of the microtubules at the proximal end of the cilium. Primary cilia play a role in a variety of human cancers. Previously primary cilia structure was perturbed in cultured cell lines derived from astrocytomas/glioblastomas; however there was always some question as to whether these findings were a cell culture phenomena. In this study we confirm that disruptions in ciliogenesis at early stages do occur in GBM tumors and that these ultrastructural findings bear resemblance to those previously observed in cell cultures. This is the first study to demonstrate that defects in cilia expression and function are a true hallmark of GBM tumors and correlate with their unrestrained growth. A review of the current ultrastructural profiles in the literature provides suggestions as to the best possible candidate protein that underlies defects in the early stages of ciliogenesis within GBM tumors.

Whole-Organism Developmental Expression Profiling Identifies RAB-28 as a Novel Ciliary GTPase Associated with the BBSome and Intraflagellar Transport

PubMed Central

Sanders, Anna A. W. M.; Li, Chunmei; Kennedy, Julie; Cai, Jerry; Scheidel, Noemie; Kennedy, Breandán N.; Morin, Ryan D.; Leroux, Michel R.; Blacque, Oliver E.

2016-01-01

Primary cilia are specialised sensory and developmental signalling devices extending from the surface of most eukaryotic cells. Defects in these organelles cause inherited human disorders (ciliopathies) such as retinitis pigmentosa and Bardet-Biedl syndrome (BBS), frequently affecting many physiological and developmental processes across multiple organs. Cilium formation, maintenance and function depend on intracellular transport systems such as intraflagellar transport (IFT), which is driven by kinesin-2 and IFT-dynein motors and regulated by the Bardet-Biedl syndrome (BBS) cargo-adaptor protein complex, or BBSome. To identify new cilium-associated genes, we employed the nematode C. elegans, where ciliogenesis occurs within a short timespan during late embryogenesis when most sensory neurons differentiate. Using whole-organism RNA-Seq libraries, we discovered a signature expression profile highly enriched for transcripts of known ciliary proteins, including FAM-161 (FAM161A orthologue), CCDC-104 (CCDC104), and RPI-1 (RP1/RP1L1), which we confirm are cilium-localised in worms. From a list of 185 candidate ciliary genes, we uncover orthologues of human MAP9, YAP, CCDC149, and RAB28 as conserved cilium-associated components. Further analyses of C. elegans RAB-28, recently associated with autosomal-recessive cone-rod dystrophy, reveal that this small GTPase is exclusively expressed in ciliated neurons where it dynamically associates with IFT trains. Whereas inactive GDP-bound RAB-28 displays no IFT movement and diffuse localisation, GTP-bound (activated) RAB-28 concentrates at the periciliary membrane in a BBSome-dependent manner and undergoes bidirectional IFT. Functional analyses reveal that whilst cilium structure, sensory function and IFT are seemingly normal in a rab-28 null allele, overexpression of predicted GDP or GTP locked variants of RAB-28 perturbs cilium and sensory pore morphogenesis and function. Collectively, our findings present a new approach for identifying ciliary proteins, and unveil RAB28, a GTPase most closely related to the BBS protein RABL4/IFT27, as an IFT-associated cargo with BBSome-dependent cell autonomous and non-autonomous functions at the ciliary base. PMID:27930654

Whole-Organism Developmental Expression Profiling Identifies RAB-28 as a Novel Ciliary GTPase Associated with the BBSome and Intraflagellar Transport.

PubMed

Jensen, Victor L; Carter, Stephen; Sanders, Anna A W M; Li, Chunmei; Kennedy, Julie; Timbers, Tiffany A; Cai, Jerry; Scheidel, Noemie; Kennedy, Breandán N; Morin, Ryan D; Leroux, Michel R; Blacque, Oliver E

2016-12-01

Primary cilia are specialised sensory and developmental signalling devices extending from the surface of most eukaryotic cells. Defects in these organelles cause inherited human disorders (ciliopathies) such as retinitis pigmentosa and Bardet-Biedl syndrome (BBS), frequently affecting many physiological and developmental processes across multiple organs. Cilium formation, maintenance and function depend on intracellular transport systems such as intraflagellar transport (IFT), which is driven by kinesin-2 and IFT-dynein motors and regulated by the Bardet-Biedl syndrome (BBS) cargo-adaptor protein complex, or BBSome. To identify new cilium-associated genes, we employed the nematode C. elegans, where ciliogenesis occurs within a short timespan during late embryogenesis when most sensory neurons differentiate. Using whole-organism RNA-Seq libraries, we discovered a signature expression profile highly enriched for transcripts of known ciliary proteins, including FAM-161 (FAM161A orthologue), CCDC-104 (CCDC104), and RPI-1 (RP1/RP1L1), which we confirm are cilium-localised in worms. From a list of 185 candidate ciliary genes, we uncover orthologues of human MAP9, YAP, CCDC149, and RAB28 as conserved cilium-associated components. Further analyses of C. elegans RAB-28, recently associated with autosomal-recessive cone-rod dystrophy, reveal that this small GTPase is exclusively expressed in ciliated neurons where it dynamically associates with IFT trains. Whereas inactive GDP-bound RAB-28 displays no IFT movement and diffuse localisation, GTP-bound (activated) RAB-28 concentrates at the periciliary membrane in a BBSome-dependent manner and undergoes bidirectional IFT. Functional analyses reveal that whilst cilium structure, sensory function and IFT are seemingly normal in a rab-28 null allele, overexpression of predicted GDP or GTP locked variants of RAB-28 perturbs cilium and sensory pore morphogenesis and function. Collectively, our findings present a new approach for identifying ciliary proteins, and unveil RAB28, a GTPase most closely related to the BBS protein RABL4/IFT27, as an IFT-associated cargo with BBSome-dependent cell autonomous and non-autonomous functions at the ciliary base.

An inverted micro-mixer based on a magnetically-actuated cilium made of Fe doped PDMS

NASA Astrophysics Data System (ADS)

Liu, Fengli; Zhang, Jun; Alici, Gursel; Yan, Sheng; Mutlu, Rahim; Li, Weihua; Yan, Tianhong

2016-09-01

In this paper, we report a new micromixer based on a flexible artificial cilium activated by an external magnetic field. The cilium is fabricated from Polydimethylsiloxane doped with Fe microparticles. The fabrication method is based on the standard sacrificial layer technology. The cilium was built on a glass slide, and then was bonded on the top of the micro-mixer chamber in a microfluidic chip. This fabrication process for the miniaturized active mixers is simple and cost effective. An electromagnetic system was used to drive the cilium and induce strong convective flows of the fluid in the chamber. In the presence of an alternating magnetic field, the cilium applied a corresponding alternating force on the surrounding fluids. The performance of the electromagnetically activated cilium was quantified and optimized in order to obtain maximum mixing performance. In addition, the mixing performance of the cilium in a circular micro-chamber was compared with pure diffusion. Up to 80% of a 60 ul liquid in the chamber can be fully mixed after 2 min using a cilium mixer under a magnetic flux density of 22 mT in contrast to the 20 min which were needed to obtain the same mixing percentage under pure diffusion. Furthermore, for a mixing degree of 80%, the mixing speed for the cilia micromixer proposed in this study was 9 times faster than that of the diffusion-based micro-mixers reported in the literature.

Robust hypothesis tests for detecting statistical evidence of two-dimensional and three-dimensional interactions in single-molecule measurements

NASA Astrophysics Data System (ADS)

Calderon, Christopher P.; Weiss, Lucien E.; Moerner, W. E.

2014-05-01

Experimental advances have improved the two- (2D) and three-dimensional (3D) spatial resolution that can be extracted from in vivo single-molecule measurements. This enables researchers to quantitatively infer the magnitude and directionality of forces experienced by biomolecules in their native environment. Situations where such force information is relevant range from mitosis to directed transport of protein cargo along cytoskeletal structures. Models commonly applied to quantify single-molecule dynamics assume that effective forces and velocity in the x ,y (or x ,y,z) directions are statistically independent, but this assumption is physically unrealistic in many situations. We present a hypothesis testing approach capable of determining if there is evidence of statistical dependence between positional coordinates in experimentally measured trajectories; if the hypothesis of independence between spatial coordinates is rejected, then a new model accounting for 2D (3D) interactions can and should be considered. Our hypothesis testing technique is robust, meaning it can detect interactions, even if the noise statistics are not well captured by the model. The approach is demonstrated on control simulations and on experimental data (directed transport of intraflagellar transport protein 88 homolog in the primary cilium).

A sliding-control switch stabilizes synchronized states in a model of actuated cilia

NASA Astrophysics Data System (ADS)

Buchmann, Amy; Cortez, Ricardo; Fauci, Lisa

2017-11-01

A key function of cilia, flexible hairlike appendages located on the surface of a cell, is the transport of mucus in the lungs, where the cilia self-organize forming a metachronal wave that propels the surrounding fluid. Cilia also play an important role in the locomotion of ciliated microswimmers and other biological processes. To analyze the coordinated movement of cilia interacting through a fluid, we model each cilium as an elastic, actuated body whose beat pattern is driven by a geometric switch that drives the motion of the power and recovery strokes. The cilia are coupled to the viscous fluid using a numerical method based upon a centerline distribution of regularized Stokeslets. We first characterize the beat cycle and flow produced by a single cilium and then present results on the synchronization states between two cilia that show that the in-phase equilibrium is unstable while the anti-phase equilibrium is stable under the geometric switch model. Adding a sliding-control switching mechanism stabilizes the in-phase motion.

A Simplified Model for the Optical Force exerted on a Vertically Oriented Cilium by an Optical Trap and the Resulting Deformation

NASA Astrophysics Data System (ADS)

Lofgren, Ian; Resnick, Andrew

2014-03-01

Eukaryotic cilia are essentially whiplike structures extending from the cell body. Although their existence has been long known, their mechanical and functional properties are poorly understood. Optical traps are a non-contact method of applying a localized force to microscopic objects and an ideal tool for the study of ciliary mechanics. Starting with the discrete dipole approximation, a common means of calculating the optical force on an object that is not spherical, we tackle the problem of the optical force on a cilium. Treating the cilium as a homogeneous nonmagnetic cylinder and the electric field of the laser beam as linearly polarized results in a force applied in the direction of polarization. The force density in the polarization direction is derived from the force on an individual dipole within the cilium, which can be integrated over the volume of the cilium in order to find the total force. Utilizing Euler-Bernoulli beam theory, we integrate the force density over a cross section of the cilium and numerically solve a fourth order differential equation to obtain the final deformation of the cilium. This prediction will later be compared with experimental results to infer the mechanical stiffness of the cilium. Support from the National Institutes of Health, 1R15DK092716 is gratefully acknowledged.

[Bardet-Biedl syndrome: cilia and obesity - from genes to integrative approaches].

PubMed

Chennen, Kirsley; Scerbo, Maria Julia; Dollfus, Hélène; Poch, Olivier; Marion, Vincent

2014-11-01

The primary cilium is a specialized organelle, present at the surface of most eukaryotic cells, whose main function is to detect, integrate and transmit intra- and extra-cellular signals. Its dysfunction usually results in a group of severe clinical manifestations nowadays termed ciliopathies. The latter can be of syndromic nature with multi-organ dysfunctions and can also be associated with a morbid obese phenotype, like it is the case in the iconic ciliopathy, the Bardet Biedl syndrome (BBS). This review will discuss the contribution of the unique context offered by the emblematic BBS for understanding the mechanisms leading to obesity via the involvement of the primary cilium together with identification of novel molecular players and signaling pathways it has helped to highlight. In the current context of translational medicine and system biology, this article will also discuss the potential benefits and challenges posed by these techniques via multi-level approaches to better dissect the underlying mechanisms leading to the complex condition of obesity. © 2014 médecine/sciences – Inserm.

Breakup and then makeup: a predictive model of how cilia self-regulate hardness for posture control.

PubMed

Bandyopadhyay, Promode R; Hansen, Joshua C

2013-01-01

Functioning as sensors and propulsors, cilia are evolutionarily conserved organelles having a highly organized internal structure. How a paramecium's cilium produces off-propulsion-plane curvature during its return stroke for symmetry breaking and drag reduction is not known. We explain these cilium deformations by developing a torsional pendulum model of beat frequency dependence on viscosity and an olivo-cerebellar model of self-regulation of posture control. The phase dependence of cilia torsion is determined, and a bio-physical model of hardness control with predictive features is offered. Crossbridge links between the central microtubule pair harden the cilium during the power stroke; this stroke's end is a critical phase during which ATP molecules soften the crossbridge-microtubule attachment at the cilium inflection point where torsion is at its maximum. A precipitous reduction in hardness ensues, signaling the start of ATP hydrolysis that re-hardens the cilium. The cilium attractor basin could be used as reference for perturbation sensing.

Is paramecium swimming autonomic?

NASA Astrophysics Data System (ADS)

Bandyopadhyay, Promode R.; Toplosky, Norman; Hansen, Joshua

2010-11-01

We seek to explore if the swimming of paramecium has an underlying autonomic mechanism. Such robotic elements may be useful in capturing the disturbance field in an environment in real time. Experimental evidence is emerging that motion control neurons of other animals may be present in paramecium as well. The limit cycle determined using analog simulation of the coupled nonlinear oscillators of olivo-cerebellar dynamics (ieee joe 33, 563-578, 2008) agrees with the tracks of the cilium of a biological paramecium. A 4-motor apparatus has been built that reproduces the kinematics of the cilium motion. The motion of the biological cilium has been analyzed and compared with the results of the finite element modeling of forces on a cilium. The modeling equates applied torque at the base of the cilium with drag, the cilium stiffness being phase dependent. A low friction pendulum apparatus with a multiplicity of electromagnetic actuators is being built for verifying the maps of the attractor basin computed using the olivo-cerebellar dynamics for different initial conditions. Sponsored by ONR 33.

Breakup and then makeup: a predictive model of how cilia self-regulate hardness for posture control

NASA Astrophysics Data System (ADS)

Bandyopadhyay, Promode R.; Hansen, Joshua C.

2013-06-01

Functioning as sensors and propulsors, cilia are evolutionarily conserved organelles having a highly organized internal structure. How a paramecium's cilium produces off-propulsion-plane curvature during its return stroke for symmetry breaking and drag reduction is not known. We explain these cilium deformations by developing a torsional pendulum model of beat frequency dependence on viscosity and an olivo-cerebellar model of self-regulation of posture control. The phase dependence of cilia torsion is determined, and a bio-physical model of hardness control with predictive features is offered. Crossbridge links between the central microtubule pair harden the cilium during the power stroke; this stroke's end is a critical phase during which ATP molecules soften the crossbridge-microtubule attachment at the cilium inflection point where torsion is at its maximum. A precipitous reduction in hardness ensues, signaling the start of ATP hydrolysis that re-hardens the cilium. The cilium attractor basin could be used as reference for perturbation sensing.

Breakup and then makeup: a predictive model of how cilia self-regulate hardness for posture control

PubMed Central

Bandyopadhyay, Promode R.; Hansen, Joshua C.

2013-01-01

Functioning as sensors and propulsors, cilia are evolutionarily conserved organelles having a highly organized internal structure. How a paramecium's cilium produces off-propulsion-plane curvature during its return stroke for symmetry breaking and drag reduction is not known. We explain these cilium deformations by developing a torsional pendulum model of beat frequency dependence on viscosity and an olivo-cerebellar model of self-regulation of posture control. The phase dependence of cilia torsion is determined, and a bio-physical model of hardness control with predictive features is offered. Crossbridge links between the central microtubule pair harden the cilium during the power stroke; this stroke's end is a critical phase during which ATP molecules soften the crossbridge-microtubule attachment at the cilium inflection point where torsion is at its maximum. A precipitous reduction in hardness ensues, signaling the start of ATP hydrolysis that re-hardens the cilium. The cilium attractor basin could be used as reference for perturbation sensing. PMID:23739771

Lithium treatment elongates primary cilia in the mouse brain and in cultured cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miyoshi, Ko, E-mail: miyoshi@cc.okayama-u.ac.jp; Kasahara, Kyosuke; Miyazaki, Ikuko

2009-10-30

The molecular mechanisms underlying the therapeutic effects of lithium, a first-line antimanic mood stabilizer, have not yet been fully elucidated. Treatment of the algae Chlamydomonas reinhardtii with lithium has been shown to induce elongation of their flagella, which are analogous structures to vertebrate cilia. In the mouse brain, adenylyl cyclase 3 (AC3) and certain neuropeptide receptors colocalize to the primary cilium of neuronal cells, suggesting a chemosensory function for the primary cilium in the nervous system. Here we show that lithium treatment elongates primary cilia in the mouse brain and in cultured cells. Brain sections from mice chronically fed withmore » Li{sub 2}CO{sub 3} were subjected to immunofluorescence study. Primary cilia carrying both AC3 and the receptor for melanin-concentrating hormone (MCH) were elongated in the dorsal striatum and nucleus accumbens of lithium-fed mice, as compared to those of control animals. Moreover, lithium-treated NIH3T3 cells and cultured striatal neurons exhibited elongation of the primary cilia. The present results provide initial evidence that a psychotropic agent can affect ciliary length in the central nervous system, and furthermore suggest that lithium exerts its therapeutic effects via the upregulation of cilia-mediated MCH sensing. These findings thus contribute novel insights into the pathophysiology of bipolar mood disorder and other psychiatric diseases.« less

A FRAP-Based Method for Monitoring Molecular Transport in Ciliary Photoreceptor Cells In Vivo.

PubMed

Wunderlich, Kirsten A; Wolfrum, Uwe

2016-01-01

The outer segment of rod and cone photoreceptor cells represents a highly modified primary sensory cilium. It renews on a daily basis throughout lifetime and effective vectorial transport to the cilium is essential for the maintenance of the photoreceptor cell function. Defects in molecules of transport modules lead to severe retinal ciliopathies. We have recently established a fluorescence recovery after photobleaching (FRAP)-based method to monitor molecular trafficking in living rodent photoreceptor cells. We irreversibly bleach the fluorescence of tagged molecules (e.g. eGFP-Rhodopsin) in photoreceptor cells of native vibratome sections through the retina by high laser intensity. In the laser scanning microscope, the recovery of the fluorescent signal is monitored over time and the kinetics of movements of molecules can be quantitatively ascertained.

Fabrication and characterization of artificial hair cell sensor based on MWCNT-PDMS composite

NASA Astrophysics Data System (ADS)

Kim, Chi Yeon; Lee, Hyun Sup; Cho, Yo Han; Joh, Cheeyoung; Choi, Pyung; Park, Seong Jin

2011-06-01

The aim of this work is to design and fabricate a flow sensor using an artificial hair cell (AHC) inspired by biological hair cells of fish. The sensor consists of a single cilium structure with high aspect ratio and a mechanoreceptor using force sensitive resistor (FSR). The cilium structure is designed for capturing a drag force with direction due to flow field around the sensor and the mechanoreceptor is designed for sensing the drag force with direction from the cilium structure and converting it into an electric signal. The mechanoreceptor has a symmetric four electrodes to sense the drag force and its direction. To fabricate the single cilium structure with high aspect ratio, we have proposed a new design concept using a separated micro mold system (SMS) fabricated by the LIGA process. For a successful replication of the cilium structure, we used the hot embossing process with the help of a double-sided mold system. We used a composite of multiwall carbon nanotube and polydimethylsiloxane (MWCNT-PDMS). The performance of the mechanoreceptors was measured by a computer-controlled nanoindenter. We carried out several experiments with the sensor in the different flow rate and direction using the experimental test apparatus. To calibrate the sensor and calculate the velocity with direction based the signal from the sensor, we analyzed the coupled phenomena between flow field and the cilium structure to calculate the deflection of the cilium structure and the drag force applying to the cilium structure due to the flow field around sensor.

Dishevelled links basal body docking and orientation in ciliated epithelial cells

PubMed Central

Vladar, Eszter K.; Axelrod, Jeffrey D.

2014-01-01

Some epithelia contain cells with multiple, motile cilia that beat in a concerted fashion. New tools and experimental systems have facilitated molecular studies of cilium biogenesis and of the coordinated planar polarization of cilia that leads to their concerted motility. Recent, elegant work by Park and colleagues, using embryonic frog epidermis, demonstrates that Dishevelled (Dvl), a key regulator of both the Wnt/β-catenin and Planar Cell Polarity (PCP) pathways, controls both the docking and planar polarization of ciliary basal bodies. PMID:18819800

Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells

NASA Technical Reports Server (NTRS)

Nauli, Surya M.; Alenghat, Francis J.; Luo, Ying; Williams, Eric; Vassilev, Peter; Li, Xiaogang; Elia, Andrew E H.; Lu, Weining; Brown, Edward M.; Quinn, Stephen J.;

Mechanical signals promote osteogenic fate through a primary cilia-mediated mechanism

PubMed Central

Chen, Julia C.; Hoey, David A.; Chua, Mardonn; Bellon, Raymond; Jacobs, Christopher R.

2016-01-01

It has long been suspected, but never directly shown, that bone formed to accommodate an increase in mechanical loading is related to the creation of osteoblasts from skeletal stem cells. Indeed, biophysical stimuli potently regulate osteogenic lineage commitment in vitro. In this study, we transplanted bone marrow cells expressing green fluorescent protein, to enable lineage tracing, and subjected mice to a biophysical stimulus, to elicit a bone-forming response. We detected cells derived from transplanted progenitors embedded within the bone matrix near active bone-forming surfaces in response to loading, demonstrating for the first time, that mechanical signals enhance the homing and attachment of bone marrow cells to bone surfaces and the commitment to an osteogenic lineage of these cells in vivo. Furthermore, we used an inducible Cre/Lox recombination system to delete kinesin family member 3A (Kif3a), a gene that is essential for primary cilia formation, at will in transplanted cells and their progeny, regardless of which tissue may have incorporated them. Disruption of the mechanosensing organelle, the primary cilium in a progenitor population, significantly decreased the amount of bone formed in response to mechanical stimulation. The collective results of our study directly demonstrate that, in a novel experimental stem cell mechanobiology model, mechanical signals enhance osteogenic lineage commitment in vivo and that the primary cilium contributes to this process.—Chen, J. C., Hoey, D. A., Chua, M., Bellon, R., Jacobs, C. R. Mechanical signals promote osteogenic fate through a primary cilia-mediated mechanism. PMID:26675708

Exploration of Self-Regulation in the Natural Swimming of the Paramecium’s Cilium

DTIC Science & Technology

2012-02-01

aquatic environments. These animals propel themselves, albeit with limited maneuverability, by the synchronous motion of numerous tiny cilia...microtubule pairs are the source of cilium hardness during the power stroke ; there is a critical phase near the end of the power stroke where one cross...return stroke ; therefore, in each beat cycle, there must be a reattachment process of the cross-bridge links and re-hardening of the cilium during the

The Meckel syndrome- associated protein MKS1 functionally interacts with components of the BBSome and IFT complexes to mediate ciliary trafficking and hedgehog signaling

PubMed Central

Barrington, Chloe L.; Katsanis, Nicholas

2017-01-01

The importance of primary cilia in human health is underscored by the link between ciliary dysfunction and a group of primarily recessive genetic disorders with overlapping clinical features, now known as ciliopathies. Many of the proteins encoded by ciliopathy-associated genes are components of a handful of multi-protein complexes important for the transport of cargo to the basal body and/or into the cilium. A key question is whether different complexes cooperate in cilia formation, and whether they participate in cilium assembly in conjunction with intraflagellar transport (IFT) proteins. To examine how ciliopathy protein complexes might function together, we have analyzed double mutants of an allele of the Meckel syndrome (MKS) complex protein MKS1 and the BBSome protein BBS4. We find that Mks1; Bbs4 double mutant mouse embryos exhibit exacerbated defects in Hedgehog (Hh) dependent patterning compared to either single mutant, and die by E14.5. Cells from double mutant embryos exhibit a defect in the trafficking of ARL13B, a ciliary membrane protein, resulting in disrupted ciliary structure and signaling. We also examined the relationship between the MKS complex and IFT proteins by analyzing double mutant between Mks1 and a hypomorphic allele of the IFTB component Ift172. Despite each single mutant surviving until around birth, Mks1; Ift172avc1 double mutants die at mid-gestation, and exhibit a dramatic failure of cilia formation. We also find that Mks1 interacts genetically with an allele of Dync2h1, the IFT retrograde motor. Thus, we have demonstrated that the MKS transition zone complex cooperates with the BBSome to mediate trafficking of specific trans-membrane receptors to the cilium. Moreover, the genetic interaction of Mks1 with components of IFT machinery suggests that the transition zone complex facilitates IFT to promote cilium assembly and structure. PMID:28291807

A Wnt/beta-catenin pathway antagonist Chibby binds Cenexin at the distal end of mother centrioles and functions in primary cilia formation.

PubMed

Steere, Nathan; Chae, Vanessa; Burke, Michael; Li, Feng-Qian; Takemaru, Ken-ichi; Kuriyama, Ryoko

2012-01-01

The mother centriole of the centrosome is distinguished from immature daughter centrioles by the presence of accessory structures (distal and subdistal appendages), which play an important role in the organization of the primary cilium in quiescent cells. Primary cilia serve as sensory organelles, thus have been implicated in mediating intracellular signal transduction pathways. Here we report that Chibby (Cby), a highly conserved antagonist of the Wnt/β-catenin pathway, is a centriolar component specifically located at the distal end of the mother centriole and essential for assembly of the primary cilium. Cby appeared as a discrete dot in the middle of a ring-like structure revealed by staining with a distal appendage component of Cep164. Cby interacted with one of the appendage components, Cenexin (Cnx), which thereby abrogated the inhibitory effect of Cby on β-catenin-mediated transcriptional activation in a dose-dependent manner. Cby and Cnx did not precisely align, as Cby was detected at a more distal position than Cnx. Cnx emerged earlier than Cby during the cell cycle and was required for recruitment of Cby to the mother centriole. However, Cby was dispensable for Cnx localization to the centriole. During massive centriogenesis in in vitro cultured mouse tracheal epithelial cells, Cby and Cnx were expressed in a similar pattern, which was coincident with the expression of Foxj1. Our results suggest that Cby plays an important role in organization of both primary and motile cilia in collaboration with Cnx.

Hook2 is involved in the morphogenesis of the primary cilium

PubMed Central

Baron Gaillard, Carole L.; Pallesi-Pocachard, Emilie; Massey-Harroche, Dominique; Richard, Fabrice; Arsanto, Jean-Pierre; Chauvin, Jean-Paul; Lecine, Patrick; Krämer, Helmut; Borg, Jean-Paul; Le Bivic, André

2011-01-01

Primary cilia originate from the centrosome and play essential roles in several cellular, developmental, and pathological processes, but the underlying mechanisms of ciliogenesis are not fully understood. Given the involvement of the adaptor protein Hook2 in centrosomal homeostasis and protein transport to pericentrosomal aggresomes, we explored its role in ciliogenesis. We found that in human retinal epithelial cells, Hook2 localizes at the Golgi apparatus and centrosome/basal body, a strategic partitioning for ciliogenesis. Of importance, Hook2 depletion disrupts ciliogenesis at a stage before the formation of the ciliary vesicle at the distal tip of the mother centriole. Using two hybrid and immunoprecipitation assays and a small interfering RNA strategy, we found that Hook2 interacts with and stabilizes pericentriolar material protein 1 (PCM1), which was reported to be essential for the recruitment of Rab8a, a GTPase that is believed to be crucial for membrane transport to the primary cilium. Of interest, GFP::Rab8a coimmunoprecipitates with endogenous Hook2 and PCM1. Finally, GFP::Rab8a can overcome Hook2 depletion, demonstrating a functional interaction between Hook2 and these two important regulators of ciliogenesis. The data indicate that Hook2 interacts with PCM1 in a complex that also contains Rab8a and regulates a limiting step required for further initiation of ciliogenesis after centriole maturation. PMID:21998199

Artificial Hair Cells for Sensing Flows

NASA Technical Reports Server (NTRS)

Chen, Jack

2007-01-01

The purpose of this article is to present additional information about the flow-velocity sensors described briefly in the immediately preceding article. As noted therein, these sensors can be characterized as artificial hair cells that implement an approximation of the sensory principle of flow-sensing cilia of fish: A cilium is bent by an amount proportional to the flow to which it is exposed. A nerve cell at the base of the cilium senses the flow by sensing the bending of the cilium. In an artificial hair cell, the artificial cilium is a microscopic cantilever beam, and the bending of an artificial cilium is measured by means of a strain gauge at its base (see Figure 1). Figure 2 presents cross sections of a representative sensor of this type at two different stages of its fabrication process. The process consists of relatively- low-temperature metallization, polymer-deposition, microfabrication, and surface-micromachining subprocesses, including plastic-deformation magnetic assembly (PDMA), which is described below. These subprocesses are suitable for a variety of substrate materials, including silicon, some glasses, and some polymers. Moreover, because it incorporates a polymeric supporting structure, this sensor is more robust, relative to its silicon-based counterparts.

Simulations of optically switchable molecular machines for particle transport.

PubMed

Raeker, Tim; Jansen, Björn; Behrens, Dominik; Hartke, Bernd

2018-03-24

A promising application for design and deployment of molecular machines is nanoscale transport, driven by artificial cilia. In this contribution, we present several further steps toward this goal, beyond our first-generation artificial cilium (Raeker et al., J. Phys. Chem. A 2012, 116, 11241). Promising new azobenzene-derivatives were tested for use as cilium motors. Using a QM/MM partitioning in on-the-fly photodynamics, excited-state surface-hopping trajectories were calculated for each isomerization direction and each motor version. The methods used were reparametrized semiempirical quantum chemistry together with floating-occupation configuration interaction as the QM part and the OPLSAA-L forcefield as MM part. In addition, we simulated actual particle transport by a single cilium attached to a model surface, with varying attachment strengths and modes, and with transport targets ranging from single atoms to multi-molecule arrangements. Our results provide valuable design guidelines for cilia-driven nanoscale transport and emphasize the need to carefully select the whole setup (not just the cilium itself, but also its surface attachment and the dynamic cilium-target interaction) to achieve true transport. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

The Leishmania major BBSome subunit BBS1 is essential for parasite virulence in the mammalian host

PubMed Central

Price, Helen P; Paape, Daniel; Hodgkinson, Michael R; Farrant, Katie; Doehl, Johannes; Stark, Meg; Smith, Deborah F

2013-01-01

Summary Bardet–Biedl syndrome (BBS) is a human genetic disorder with a spectrum of symptoms caused by primary cilium dysfunction. The disease is caused by mutations in one of at least 17 identified genes, of which seven encode subunits of the BBSome, a protein complex required for specific trafficking events to and from the primary cilium. The molecular mechanisms associated with BBSome function remain to be fully elucidated. Here, we generated null and complemented mutants of the BBSome subunit BBS1 in the protozoan parasite, Leishmania. In the absence of BBS1, extracellular parasites have no apparent defects in growth, flagellum assembly, motility or differentiation in vitro but there is accumulation of vacuole-like structures close to the flagellar pocket. Infectivity of these parasites for macrophages in vitro is reduced compared with wild-type controls but the null parasites retain the ability to differentiate to the intracellular amastigote stage. However, infectivity of BBS1 null parasites is severely compromised in a BALB/c mouse footpad model. We hypothesize that the absence of BBS1 in Leishmania leads to defects in specific trafficking events that affect parasite persistence in the host. This is the first report of an association between the BBSome complex and pathogen infectivity. PMID:23998526

From damage response to action potentials: early evolution of neural and contractile modules in stem eukaryotes.

PubMed

Brunet, Thibaut; Arendt, Detlev

2016-01-05

Eukaryotic cells convert external stimuli into membrane depolarization, which in turn triggers effector responses such as secretion and contraction. Here, we put forward an evolutionary hypothesis for the origin of the depolarization-contraction-secretion (DCS) coupling, the functional core of animal neuromuscular circuits. We propose that DCS coupling evolved in unicellular stem eukaryotes as part of an 'emergency response' to calcium influx upon membrane rupture. We detail how this initial response was subsequently modified into an ancient mechanosensory-effector arc, present in the last eukaryotic common ancestor, which enabled contractile amoeboid movement that is widespread in extant eukaryotes. Elaborating on calcium-triggered membrane depolarization, we reason that the first action potentials evolved alongside the membrane of sensory-motile cilia, with the first voltage-sensitive sodium/calcium channels (Nav/Cav) enabling a fast and coordinated response of the entire cilium to mechanosensory stimuli. From the cilium, action potentials then spread across the entire cell, enabling global cellular responses such as concerted contraction in several independent eukaryote lineages. In animals, this process led to the invention of mechanosensory contractile cells. These gave rise to mechanosensory receptor cells, neurons and muscle cells by division of labour and can be regarded as the founder cell type of the nervous system. © 2015 The Authors.

From damage response to action potentials: early evolution of neural and contractile modules in stem eukaryotes

PubMed Central

Brunet, Thibaut; Arendt, Detlev

2016-01-01

Eukaryotic cells convert external stimuli into membrane depolarization, which in turn triggers effector responses such as secretion and contraction. Here, we put forward an evolutionary hypothesis for the origin of the depolarization–contraction–secretion (DCS) coupling, the functional core of animal neuromuscular circuits. We propose that DCS coupling evolved in unicellular stem eukaryotes as part of an ‘emergency response’ to calcium influx upon membrane rupture. We detail how this initial response was subsequently modified into an ancient mechanosensory–effector arc, present in the last eukaryotic common ancestor, which enabled contractile amoeboid movement that is widespread in extant eukaryotes. Elaborating on calcium-triggered membrane depolarization, we reason that the first action potentials evolved alongside the membrane of sensory-motile cilia, with the first voltage-sensitive sodium/calcium channels (Nav/Cav) enabling a fast and coordinated response of the entire cilium to mechanosensory stimuli. From the cilium, action potentials then spread across the entire cell, enabling global cellular responses such as concerted contraction in several independent eukaryote lineages. In animals, this process led to the invention of mechanosensory contractile cells. These gave rise to mechanosensory receptor cells, neurons and muscle cells by division of labour and can be regarded as the founder cell type of the nervous system. PMID:26598726

Simulations of centriole of polarized centrosome as a monopole antenna in immune and viral synapses.

PubMed

Dvorak, Josef; Melichar, Bohuslav; Filipova, Alzbeta; Grimova, Jana; Grimova, Nela; Rozsypalova, Aneta; Buka, David; Voboril, Rene; Zapletal, Radek; Buchler, Tomas; Richter, Igor; Buka, David

2018-01-01

The immune synapse (IS) is a temporary interface between an antigen-presenting cell and an effector lymphocyte. Viral synapse is a molecularly organized cellular junction that is structurally similar to the IS. Primary cilium is considered as a functional homologue of the IS due to the morphological and functional similarities in architecture between both micotubule structures. It has been hypothesized that endogenous electromagnetic field in the cell is generated by a unique cooperating system between mitochondria and microtubules. We are extending this prior hypothesis of the endogenous electromagnetic field in the cell postulating that polarized centriole in immune and viral synapse could serve as a monopole antenna. This is an addition to our hypothesis that primary cilium could serve as a monopole antenna. We simulated the distribution of electric field of centriole of polarized centrosome as a monopole antenna in immune and viral synapse. Very weak electromagnetic field of polarized centriole of CD8+ T lymphocyte in IS can contribute to the transport of cytolytic granules into the attacked (cancer) cell. Analogically, very weak electromagnetic field of polarized centriole in viral synapse of infected CD4 cells can aid the transport of viruses (human immunodeficiency virus) to non-infected CD4 cells. We hypothesized that healthy organisms need these monopole antennas. If, during the neoplastic transformation, healthy cells lose monopole antennas in form of primary cilia, the IS aims to replace them by monopole antennas of polarized centrioles in IS to restore homeostasis.

Abnormal photoreceptor outer segment development and early retinal degeneration in kif3a mutant zebrafish.

PubMed

Raghupathy, Rakesh K; Zhang, Xun; Alhasani, Reem H; Zhou, Xinzhi; Mullin, Margaret; Reilly, James; Li, Wenchang; Liu, Mugen; Shu, Xinhua

2016-08-01

Photoreceptors are highly specialized sensory neurons that possess a modified primary cilium called the outer segment. Photoreceptor outer segment formation and maintenance require highly active protein transport via a process known as intraflagellar transport. Anterograde transport in outer segments is powered by the heterotrimeric kinesin II and coordinated by intraflagellar transport proteins. Here, we describe a new zebrafish model carrying a nonsense mutation in the kinesin II family member 3A (kif3a) gene. Kif3a mutant zebrafish exhibited curved body axes and kidney cysts. Outer segments were not formed in most parts of the mutant retina, and rhodopsin was mislocalized, suggesting KIF3A has a role in rhodopsin trafficking. Both rod and cone photoreceptors degenerated rapidly between 4 and 9 days post fertilization, and electroretinography response was not detected in 7 days post fertilization mutant larvae. Loss of KIF3A in zebrafish also resulted in an intracellular transport defect affecting anterograde but not retrograde transport of organelles. Our results indicate KIF3A plays a conserved role in photoreceptor outer segment formation and intracellular transport. Copyright © 2016 John Wiley & Sons, Ltd.

Mice Deficient in the Axonemal Protein Tektin-t Exhibit Male Infertility and Immotile-Cilium Syndrome Due to Impaired Inner Arm Dynein Function

PubMed Central

Tanaka, Hiromitsu; Iguchi, Naoko; Toyama, Yoshiro; Kitamura, Kouichi; Takahashi, Tohru; Kaseda, Kazuhiro; Maekawa, Mamiko; Nishimune, Yoshitake

2004-01-01

The haploid germ cell-specific Tektin-t protein is a member of the Tektin family of proteins that form filaments in flagellar, ciliary, and axonemal microtubules. To investigate the physiological role of Tektin-t, we generated mice with a mutation in the tektin-t gene. The homozygous mutant males were infertile, while the females were fully fertile. Sperm morphology and function were abnormal, with frequent bending of the sperm flagella and marked defects in motility. In vitro fertilization assays showed that the defective spermatozoa were able to fertilize eggs. Electron microscopic examination showed that the dynein inner arm structure was disrupted in the sperm flagella of tektin-t-deficient mice. Furthermore, homozygous mutant mice had functionally defective tracheal cilia, as evidenced by altered dynein arm morphology. These results indicate that Tektin-t participates in dynein inner arm formation or attachment and that the loss of Tektin-t results in impaired motility of both flagella and cilia. Therefore, the tektin-t gene is one of the causal genes for immotile-cilium syndrome/primary ciliary dyskinesia. PMID:15340058

APC sets the Wnt tone necessary for cerebral cortical progenitor development

PubMed Central

Nakagawa, Naoki; Li, Jingjun; Yabuno-Nakagawa, Keiko; Eom, Tae-Yeon; Cowles, Martis; Mapp, Tavien; Taylor, Robin; Anton, E.S.

2017-01-01

Adenomatous polyposis coli (APC) regulates the activity of β-catenin, an integral component of Wnt signaling. However, the selective role of the APC–β-catenin pathway in cerebral cortical development is unknown. Here we genetically dissected the relative contributions of APC-regulated β-catenin signaling in cortical progenitor development, a necessary early step in cerebral cortical formation. Radial progenitor-specific inactivation of the APC–β-catenin pathway indicates that the maintenance of appropriate β-catenin-mediated Wnt tone is necessary for the orderly differentiation of cortical progenitors and the resultant formation of the cerebral cortex. APC deletion deregulates β-catenin, leads to high Wnt tone, and disrupts Notch1 signaling and primary cilium maintenance necessary for radial progenitor functions. β-Catenin deregulation directly disrupts cilium maintenance and signaling via Tulp3, essential for intraflagellar transport of ciliary signaling receptors. Surprisingly, deletion of β-catenin or inhibition of β-catenin activity in APC-null progenitors rescues the APC-null phenotype. These results reveal that APC-regulated β-catenin activity in cortical progenitors sets the appropriate Wnt tone necessary for normal cerebral cortical development. PMID:28916710

Clinical and molecular features of Joubert syndrome and related disorders

PubMed Central

Parisi, Melissa A.

2009-01-01

Joubert syndrome (JBTS; OMIM 213300) is a rare, autosomal recessive disorder characterized by a specific congenital malformation of the hindbrain and a broad spectrum of other phenotypic findings that is now known to be caused by defects in the structure and/or function of the primary cilium. The complex hindbrain malformation that is characteristic of JBTS can be identified on axial magnetic resonance imaging and is known as the molar tooth sign (MTS); other diagnostic criteria include intellectual disability, hypotonia, and often, abnormal respiratory pattern and/or abnormal eye movements. In addition, a broad spectrum of other anomalies characterize Joubert syndrome and related disorders (JSRD), and may include retinal dystrophy, ocular coloboma, oral frenulae and tongue tumors, polydactyly, cystic renal disease (including cystic dysplasia or juvenile nephronophthisis), and congenital hepatic fibrosis. The clinical course can be variable, but most children with this condition survive infancy to reach adulthood. At least 8 genes cause JSRD, with some genotype-phenotype correlations emerging, including the association between mutations in the MKS3 gene and hepatic fibrosis characteristic of the JSRD subtype known as COACH syndrome. Several of the causative genes for JSRD are implicated in other ciliary disorders, such as juvenile nephronophthisis and Meckel syndrome, illustrating the close association between these conditions and their overlapping clinical features that reflect a shared etiology involving the primary cilium. PMID:19876931

Reduction of the immunostainable length of the hippocampal dentate granule cells' primary cilia in 3xAD-transgenic mice producing human A{beta}{sub 1-42} and tau

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chakravarthy, Balu, E-mail: Balu.Chakravarthy@nrc-cnrc.gc.ca; Gaudet, Chantal; Menard, Michel

2012-10-12

Highlights: Black-Right-Pointing-Pointer A{beta} and tau-induced neurofibrillary tangles play a key role in Alzheimer's disease. Black-Right-Pointing-Pointer A{beta}{sub 1-42} and mutant tau protein together reduce the primary cilium length. Black-Right-Pointing-Pointer This shortening likely reduces cilium-dependent neurogenesis and memory function. Black-Right-Pointing-Pointer This provides a model of an A{beta}/tau targeting of a neuronal signaling organelle. -- Abstract: The hippocampal dentate gyrus is one of the two sites of continuous neurogenesis in adult rodents and humans. Virtually all dentate granule cells have a single immobile cilium with a microtubule spine or axoneme covered with a specialized cell membrane loaded with receptors such as the somatostatinmore » receptor 3 (SSTR3), and the p75 neurotrophin receptor (p75{sup NTR}). The signals from these receptors have been reported to stimulate neuroprogenitor proliferation and the post-mitotic maturation of newborn granule cells into functioning granule cells. We have found that in 6-24-months-old triple transgenic Alzheimer's disease model mice (3xTg-AD) producing both A{beta}{sub 1-42} and the mutant human tau protein tau{sub P301L,} the dentate granule cells still had immunostainable SSTR3- and p75{sup NTR}-bearing cilia but they were only half the length of the immunostained cilia in the corresponding wild-type mice. However, the immunostainable length of the granule cell cilia was not reduced either in 2xTg-AD mice accumulating large amounts of A{beta}{sub 1-42} or in mice accumulating only a mutant human tau protein. Thus it appears that a combination of A{beta}{sub 1-42} and tau protein accumulation affects the levels of functionally important receptors in 3xTg-AD mice. These observations raise the important possibility that structural and functional changes in granule cell cilia might have a role in AD.« less

A novel murine allele of Intraflagellar Transport Protein 172 causes a syndrome including VACTERL-like features with hydrocephalus.

PubMed

Friedland-Little, Joshua M; Hoffmann, Andrew D; Ocbina, Polloneal Jymmiel R; Peterson, Mike A; Bosman, Joshua D; Chen, Yan; Cheng, Steven Y; Anderson, Kathryn V; Moskowitz, Ivan P

2011-10-01

The primary cilium is emerging as a crucial regulator of signaling pathways central to vertebrate development and human disease. We identified atrioventricular canal 1 (avc1), a mouse mutation that caused VACTERL association with hydrocephalus, or VACTERL-H. We showed that avc1 is a hypomorphic mutation of intraflagellar transport protein 172 (Ift172), required for ciliogenesis and Hedgehog (Hh) signaling. Phenotypically, avc1 caused VACTERL-H but not abnormalities in left-right (L-R) axis formation. Avc1 resulted in structural cilia defects, including truncated cilia in vivo and in vitro. We observed a dose-dependent requirement for Ift172 in ciliogenesis using an allelic series generated with Ift172(avc1) and Ift172(wim), an Ift172 null allele: cilia were present on 42% of avc1 mouse embryonic fibroblast (MEF) and 28% of avc1/wim MEFs, in contrast to >90% of wild-type MEFs. Furthermore, quantitative cilium length analysis identified two specific cilium populations in mutant MEFS: a normal population with normal IFT and a truncated population, 50% of normal length, with disrupted IFT. Cells from wild-type embryos had predominantly full-length cilia, avc1 embryos, with Hh signaling abnormalities but not L-R abnormalities, had cilia equally divided between full-length and truncated, and avc1/wim embryos, with both Hh signaling and L-R abnormalities, were primarily truncated. Truncated Ift172 mutant cilia showed defects of the distal ciliary axoneme, including disrupted IFT88 localization and Hh-dependent Gli2 localization. We propose a model in which mutation of Ift172 results in a specific class of abnormal cilia, causing disrupted Hh signaling while maintaining L-R axis determination, and resulting in the VACTERL-H phenotype.

Force-response considerations in ciliary mechanosensation.

PubMed

Resnick, Andrew; Hopfer, Ulrich

2007-08-15

Considerable experimental evidence indicates that the primary, nonmotile cilium is a mechanosensory organelle in several epithelial cell types. As the relationship between cellular responses and nature and magnitude of applied forces is not well understood, we have investigated the effects of exposure of monolayers of renal collecting duct chief cells to orbital shaking and quantified the forces incident on cilia. An exposure of 24 h of these cells to orbital shaking resulted in a decrease of amiloride-sensitive sodium current by approximately 60% and ciliary length by approximately 30%. The sensitivity of the sodium current to shaking was dependent on intact cilia. The drag force on cilia due to induced fluid flow during orbital shaking was estimated at maximally 5.2x10(-3) pN at 2 Hz, approximately 4 times that of thermal noise. The major structural feature of cilia contributing to their sensitivity appears to be ciliary length. As more than half of the total drag force is exerted on the ciliary cap, one function of the slender stalk may be to expose the cap to greater drag force. Regardless, the findings indicate that the cilium is a mechanosensory organelle with a sensitivity much lower than previously recognized.

APC sets the Wnt tone necessary for cerebral cortical progenitor development.

PubMed

Nakagawa, Naoki; Li, Jingjun; Yabuno-Nakagawa, Keiko; Eom, Tae-Yeon; Cowles, Martis; Mapp, Tavien; Taylor, Robin; Anton, E S

2017-08-15

Adenomatous polyposis coli (APC) regulates the activity of β-catenin, an integral component of Wnt signaling. However, the selective role of the APC-β-catenin pathway in cerebral cortical development is unknown. Here we genetically dissected the relative contributions of APC-regulated β-catenin signaling in cortical progenitor development, a necessary early step in cerebral cortical formation. Radial progenitor-specific inactivation of the APC-β-catenin pathway indicates that the maintenance of appropriate β-catenin-mediated Wnt tone is necessary for the orderly differentiation of cortical progenitors and the resultant formation of the cerebral cortex. APC deletion deregulates β-catenin, leads to high Wnt tone, and disrupts Notch1 signaling and primary cilium maintenance necessary for radial progenitor functions. β-Catenin deregulation directly disrupts cilium maintenance and signaling via Tulp3, essential for intraflagellar transport of ciliary signaling receptors. Surprisingly, deletion of β-catenin or inhibition of β-catenin activity in APC-null progenitors rescues the APC-null phenotype. These results reveal that APC-regulated β-catenin activity in cortical progenitors sets the appropriate Wnt tone necessary for normal cerebral cortical development. © 2017 Nakagawa et al.; Published by Cold Spring Harbor Laboratory Press.

Large-scale Synchronization in Carpets of Micro-rotors

NASA Astrophysics Data System (ADS)

Kanale, Anup; Guo, Hanliang; Yan, Wen; Kanso, Eva

2017-11-01

Motile cilia are ubiquitous in nature, and have a critical role in biological locomotion and fluid transport. They often beat in an orchestrated wavelike fashion, and theoretical evidence suggests that this coordinated motion could arise from hydrodynamic interactions. Models based on bead-spring oscillators were used to examine the interaction between pairs of cilia, focusing on in-phase or anti-phase synchrony, while models of hydrodynamically-coupled elastic filaments looked at metachronal coordination in large but finite numbers of interacting cilia. The latter models reproduce metachronal wave coordination, but they are not readily amenable to analysis and parametric studies that highlight the origin of the instabilities that lead to wave propagations and wavelength selection. Here, we use a known model in which each cilium is represented by a rigid sphere moving along a circular trajectory close to a wall, hence the term rotor. The rotor is driven by a cilia-inspired force profile. We generalize this model to a doubly-periodic array of rotors, assuming small distance to the bounding wall, and employ Ewald summation techniques to solve for the flow field. Our goal is to examine the conditions that give rise to stable metachronal waves and their associated wavelength.

Further Insights into the Ciliary Gene and Protein KIZ and Its Murine Ortholog PLK1S1 Mutated in Rod-Cone Dystrophy

PubMed Central

Méjécase, Cécile; Bertelli, Matteo; Terray, Angélique; Michiels, Christelle; Condroyer, Christel; Fouquet, Stéphane; Sadoun, Maxime; Clérin, Emmanuelle; Liu, Binqian; Léveillard, Thierry; Goureau, Olivier; Sahel, José-Alain; Audo, Isabelle

2017-01-01

We identified herein additional patients with rod-cone dystrophy (RCD) displaying mutations in KIZ, encoding the ciliary centrosomal protein kizuna and performed functional characterization of the respective protein in human fibroblasts and of its mouse ortholog PLK1S1 in the retina. Mutation screening was done by targeted next generation sequencing and subsequent Sanger sequencing validation. KIZ mRNA levels were assessed on blood and serum-deprived human fibroblasts from a control individual and a patient, compound heterozygous for the c.52G>T (p.Glu18*) and c.119_122del (p.Lys40Ilefs*14) mutations in KIZ. KIZ localization, documentation of cilium length and immunoblotting were performed in these two fibroblast cell lines. In addition, PLK1S1 immunolocalization was conducted in mouse retinal cryosections and isolated rod photoreceptors. Analyses of additional RCD patients enabled the identification of two homozygous mutations in KIZ, the known c.226C>T (p.Arg76*) mutation and a novel variant, the c.3G>A (p.Met1?) mutation. Albeit the expression levels of KIZ were three-times lower in the patient than controls in whole blood cells, further analyses in control- and mutant KIZ patient-derived fibroblasts unexpectedly revealed no significant difference between the two genotypes. Furthermore, the averaged monocilia length in the two fibroblast cell lines was similar, consistent with the preserved immunolocalization of KIZ at the basal body of the primary cilia. Analyses in mouse retina and isolated rod photoreceptors showed PLK1S1 localization at the base of the photoreceptor connecting cilium. In conclusion, two additional patients with mutations in KIZ were identified, further supporting that defects in KIZ/PLK1S1, detected at the basal body of the primary cilia in fibroblasts, and the photoreceptor connecting cilium in mouse, respectively, are involved in RCD. However, albeit the mutations were predicted to lead to nonsense mediated mRNA decay, we could not detect changes upon expression levels, protein localization or cilia length in KIZ-mutated fibroblast cells. Together, our findings unveil the limitations of fibroblasts as a cellular model for RCD and call for other models such as induced pluripotent stem cells to shed light on retinal pathogenic mechanisms of KIZ mutations. PMID:29057815

Short-Rib Polydactyly and Jeune Syndromes Are Caused by Mutations in WDR60

PubMed Central

McInerney-Leo, Aideen M.; Schmidts, Miriam; Cortés, Claudio R.; Leo, Paul J.; Gener, Blanca; Courtney, Andrew D.; Gardiner, Brooke; Harris, Jessica A.; Lu, Yeping; Marshall, Mhairi; Scambler, Peter J.; Beales, Philip L.; Brown, Matthew A.; Zankl, Andreas; Mitchison, Hannah M.; Duncan, Emma L.; Wicking, Carol

2013-01-01

Short-rib polydactyly syndromes (SRPS I–V) are a group of lethal congenital disorders characterized by shortening of the ribs and long bones, polydactyly, and a range of extraskeletal phenotypes. A number of other disorders in this grouping, including Jeune and Ellis-van Creveld syndromes, have an overlapping but generally milder phenotype. Collectively, these short-rib dysplasias (with or without polydactyly) share a common underlying defect in primary cilium function and form a subset of the ciliopathy disease spectrum. By using whole-exome capture and massive parallel sequencing of DNA from an affected Australian individual with SRPS type III, we detected two novel heterozygous mutations in WDR60, a relatively uncharacterized gene. These mutations segregated appropriately in the unaffected parents and another affected family member, confirming compound heterozygosity, and both were predicted to have a damaging effect on the protein. Analysis of an additional 54 skeletal ciliopathy exomes identified compound heterozygous mutations in WDR60 in a Spanish individual with Jeune syndrome of relatively mild presentation. Of note, these two families share one novel WDR60 missense mutation, although haplotype analysis suggested no shared ancestry. We further show that WDR60 localizes at the base of the primary cilium in wild-type human chondrocytes, and analysis of fibroblasts from affected individuals revealed a defect in ciliogenesis and aberrant accumulation of the GLI2 transcription factor at the centrosome or basal body in the absence of an obvious axoneme. These findings show that WDR60 mutations can cause skeletal ciliopathies and suggest a role for WDR60 in ciliogenesis. PMID:23910462

Meckel-Gruber Syndrome: An Update on Diagnosis, Clinical Management, and Research Advances.

PubMed

Hartill, Verity; Szymanska, Katarzyna; Sharif, Saghira Malik; Wheway, Gabrielle; Johnson, Colin A

2017-01-01

Meckel-Gruber syndrome (MKS) is a lethal autosomal recessive congenital anomaly syndrome caused by mutations in genes encoding proteins that are structural or functional components of the primary cilium. Conditions that are caused by mutations in ciliary genes are collectively termed the ciliopathies, and MKS represents the most severe condition in this group of disorders. The primary cilium is a microtubule-based organelle, projecting from the apical surface of vertebrate cells. It acts as an "antenna" that receives and transduces chemosensory and mechanosensory signals, but also regulates diverse signaling pathways, such as Wnt and Shh, that have important roles during embryonic development. Most MKS proteins localize to a distinct ciliary compartment called the transition zone (TZ) that regulates the trafficking of cargo proteins or lipids. In this review, we provide an up-to-date summary of MKS clinical features, molecular genetics, and clinical diagnosis. MKS has a highly variable phenotype, extreme genetic heterogeneity, and displays allelism with other related ciliopathies such as Joubert syndrome, presenting significant challenges to diagnosis. Recent advances in genetic technology, with the widespread use of multi-gene panels for molecular testing, have significantly improved diagnosis, genetic counseling, and the clinical management of MKS families. These include the description of some limited genotype-phenotype correlations. We discuss recent insights into the molecular basis of disease in MKS, since the functions of some of the relevant ciliary proteins have now been determined. A common molecular etiology appears to be disruption of ciliary TZ structure and function, affecting essential developmental signaling and the regulation of secondary messengers.

Defective ciliogenesis, embryonic lethality and severe impairment of the Sonic Hedgehog pathway caused by inactivation of the mouse complex A intraflagellar transport gene Ift122/Wdr10, partially overlapping with the DNA repair gene Med1/Mbd4

PubMed Central

Cortellino, Salvatore; Wang, Chengbing; Wang, Baolin; Bassi, Maria Rosaria; Caretti, Elena; Champeval, Delphine; Calmont, Amelie; Jarnik, Michal; Burch, John; Zaret, Kenneth; Larue, Lionel; Bellacosa, Alfonso

2009-01-01

Primary cilia are assembled and maintained by evolutionarily conserved intraflagellar transport (IFT) proteins that are involved in the coordinated movement of macromolecular cargo from the basal body to the cilium tip and back. The IFT machinery is organized in two structural complexes named complex A and complex B. Recently, inactivation in the mouse germline of Ift genes belonging to complex B revealed a requirement of ciliogenesis, or proteins involved in ciliogenesis, for Sonic Hedgehog (Shh) signaling in mammals. Here we report on a complex A mutant mouse, defective for the Ift122 gene. Ift122-null embryos show multiple developmental defects (exencephaly, situs viscerum inversus, delay in turning, hemorrhage and defects in limb development) that result in lethality. In the node, primary cilia were absent or malformed in homozygous mutant and heterozygous embryos, respectively. Impairment of the Shh pathway was apparent in both neural tube patterning (expansion of motoneurons and rostro-caudal level-dependent contraction or expansion of the dorso-lateral interneurons), and limb patterning (ectrosyndactyly). These phenotypes are distinct from both complex B IFT mutant embryos and embryos defective for the ciliary protein hennin/Arl13b, and suggest reduced levels of both Gli2/Gli3 activator and Gli3 repressor functions. We conclude that complex A and complex B factors play similar but distinct roles in ciliogenesis and Shh/Gli3 signaling. PMID:19000668

Transcriptional program of ciliated epithelial cells reveals new cilium and centrosome components and links to human disease.

PubMed

Hoh, Ramona A; Stowe, Timothy R; Turk, Erin; Stearns, Tim

2012-01-01

Defects in the centrosome and cilium are associated with a set of human diseases having diverse phenotypes. To further characterize the components that define the function of these organelles we determined the transcriptional profile of multiciliated tracheal epithelial cells. Cultures of mouse tracheal epithelial cells undergoing differentiation in vitro were derived from mice expressing GFP from the ciliated-cell specific FOXJ1 promoter (FOXJ1:GFP). The transcriptional profile of ciliating GFP+ cells from these cultures was defined at an early and a late time point during differentiation and was refined by subtraction of the profile of the non-ciliated GFP- cells. We identified 649 genes upregulated early, when most cells were forming basal bodies, and 73 genes genes upregulated late, when most cells were fully ciliated. Most, but not all, of known centrosome proteins are transcriptionally upregulated early, particularly Plk4, a master regulator of centriole formation. We found that three genes associated with human disease states, Mdm1, Mlf1, and Dyx1c1, are upregulated during ciliogenesis and localize to centrioles and cilia. This transcriptome for mammalian multiciliated epithelial cells identifies new candidate centrosome and cilia proteins, highlights similarities between components of motile and primary cilia, and identifies new links between cilia proteins and human disease.

Transcriptional Program of Ciliated Epithelial Cells Reveals New Cilium and Centrosome Components and Links to Human Disease

PubMed Central

Hoh, Ramona A.; Stowe, Timothy R.; Turk, Erin; Stearns, Tim

2012-01-01

Defects in the centrosome and cilium are associated with a set of human diseases having diverse phenotypes. To further characterize the components that define the function of these organelles we determined the transcriptional profile of multiciliated tracheal epithelial cells. Cultures of mouse tracheal epithelial cells undergoing differentiation in vitro were derived from mice expressing GFP from the ciliated-cell specific FOXJ1 promoter (FOXJ1:GFP). The transcriptional profile of ciliating GFP+ cells from these cultures was defined at an early and a late time point during differentiation and was refined by subtraction of the profile of the non-ciliated GFP- cells. We identified 649 genes upregulated early, when most cells were forming basal bodies, and 73 genes genes upregulated late, when most cells were fully ciliated. Most, but not all, of known centrosome proteins are transcriptionally upregulated early, particularly Plk4, a master regulator of centriole formation. We found that three genes associated with human disease states, Mdm1, Mlf1, and Dyx1c1, are upregulated during ciliogenesis and localize to centrioles and cilia. This transcriptome for mammalian multiciliated epithelial cells identifies new candidate centrosome and cilia proteins, highlights similarities between components of motile and primary cilia, and identifies new links between cilia proteins and human disease. PMID:23300604

The Rab GTPase Rab8 as a shared regulator of ciliogenesis and immune synapse assembly: From a conserved pathway to diverse cellular structures.

PubMed

Patrussi, Laura; Baldari, Cosima T

2016-01-01

Rab GTPases, which form the largest branch of the Ras GTPase superfamily, regulate almost every step of vesicle-mediated trafficking. Among them, Rab8 is an essential participant in primary cilium formation. In a report recently published in the Journal of Cell Science, Finetti and colleagues identify Rab8 as a novel player in vesicular traffic in the non-ciliated T lymphocytes, which contributes to the assembly of the specialized signaling platform known as the immune synapse. By interacting with the v-SNARE VAMP-3, Rab8 is indeed responsible for the final docking/fusion step in T cell receptor (TCR) recycling to the immune synapse. A second important take-home message which comes to light from this work is that VAMP-3 also interacts with Rab8 at the base of the cilium in NIH-3T3 cells, where it regulates ciliary growth and targeting of Smoothened at the plasma membrane. Hence the data presented in this report, in addition to identifying Rab8 as a novel player in vesicular traffic to the immune synapse, reveal how both ciliated and non-ciliated cells take advantage of a conserved pathway to build highly specific cellular structures.

Surface topography regulates wnt signaling through control of primary cilia structure in mesenchymal stem cells

PubMed Central

McMurray, R. J.; Wann, A. K. T.; Thompson, C. L.; Connelly, J. T.; Knight, M. M.

2013-01-01

The primary cilium regulates cellular signalling including influencing wnt sensitivity by sequestering β-catenin within the ciliary compartment. Topographic regulation of intracellular actin-myosin tension can control stem cell fate of which wnt is an important mediator. We hypothesized that topography influences mesenchymal stem cell (MSC) wnt signaling through the regulation of primary cilia structure and function. MSCs cultured on grooves expressed elongated primary cilia, through reduced actin organization. siRNA inhibition of anterograde intraflagellar transport (IFT88) reduced cilia length and increased active nuclear β-catenin. Conversely, increased primary cilia assembly in MSCs cultured on the grooves was associated with decreased levels of nuclear active β-catenin, axin-2 induction and proliferation, in response to wnt3a. This negative regulation, on grooved topography, was reversed by siRNA to IFT88. This indicates that subtle regulation of IFT and associated cilia structure, tunes the wnt response controlling stem cell differentiation. PMID:24346024

Polycystic Kidney Disease: Pathogenesis and Potential Therapies

PubMed Central

Takiar, Vinita; Caplan, Michael J.

2011-01-01

Autosomal dominant polycystic kidney disease (ADPKD) is a prevalent, inherited condition for which there is currently no effective specific clinical therapy. The disease is characterized by the progressive development of fluid-filled cysts derived from renal tubular epithelial cells which gradually compress the parenchyma and compromise renal function. Current interests in the field focus on understanding and exploiting signaling mechanisms underlying disease pathogenesis as well as delineating the role of the primary cilium in cystogenesis. This review highlights the pathogenetic pathways underlying renal cyst formation as well as novel therapeutic targets for the treatment of PKD. PMID:21146605

Of cilium and flagellum kinematics

NASA Astrophysics Data System (ADS)

Bandyopadhyay, Promode R.; Hansen, Joshua C.

2009-11-01

The kinematics of propulsion of small animals such as paramecium and spermatozoa is considered. Larger scale models of the cilium and flagellum have been built and a four-motor apparatus has been constructed to reproduce their known periodic motions. The cilium model has transverse deformational ability in one plane only, while the flagellum model has such ability in two planes. When the flagellum model is given a push-pull in one diametral plane, instead of transverse deflection in one plane, it forms a coil. Berg & Anderson's postulation (Nature 245 1973) that a flagellum rotates, is recalled. The kinematics of cilia of paramecium, of the whipping motion of the spermatozoa flagella, and of the flapping motion (rolling and pitching) of the pectoral fins of much larger animals such penguins, have been reproduced in the same basic paramecium apparatus. The results suggest that each of the tiny individual paramecium propulsors have the intrinsic dormant kinematic and structural building blocks to optimize into higher Reynolds number propulsors. A synthetic hypothesis on how small might have become large is animated.

Epidermal development, growth control, and homeostasis in the face of centrosome amplification.

PubMed

Kulukian, Anita; Holland, Andrew J; Vitre, Benjamin; Naik, Shruti; Cleveland, Don W; Fuchs, Elaine

2015-11-17

As nucleators of the mitotic spindle and primary cilium, centrosomes play crucial roles in equal segregation of DNA content to daughter cells, coordination of growth and differentiation, and transduction of homeostatic cues. Whereas the majority of mammalian cells carry no more than two centrosomes per cell, exceptions to this rule apply in certain specialized tissues and in select disease states, including cancer. Centrosome amplification, or the condition of having more than two centrosomes per cell, has been suggested to contribute to instability of chromosomes, imbalance in asymmetric divisions, and reorganization of tissue architecture; however, the degree to which these conditions are a direct cause of or simply a consequence of human disease is poorly understood. Here we addressed this issue by generating a mouse model inducing centrosome amplification in a naturally proliferative epithelial tissue by elevating Polo-like kinase 4 (Plk4) expression in the skin epidermis. By altering centrosome numbers, we observed multiciliated cells, spindle orientation errors, and chromosome segregation defects within developing epidermis. None of these defects was sufficient to impart a proliferative advantage within the tissue, however. Rather, impaired mitoses led to p53-mediated cell death and contributed to defective growth and stratification. Despite these abnormalities, mice remained viable and healthy, although epidermal cells with centrosome amplification were still appreciable. Moreover, these abnormalities were insufficient to disrupt homeostasis and initiate or enhance tumorigenesis, underscoring the powerful surveillance mechanisms in the skin.

A novel approach to biocontrol: Release of live insect hosts pre-infected with entomopathogenic nematodes.

PubMed

Gumus, Arife; Karagoz, Mehmet; Shapiro-Ilan, David; Hazir, Selcuk

2015-09-01

As a new application approach, we tested the efficacy of releasing live insect hosts that were pre-infected with entomopathogenic nematodes against insect pests living in cryptic habitats. We hypothesized that the pre-infected hosts could carry the next generation of emerging nematode infective juveniles to hard-to-reach target sites, and thereby facilitate enhanced control in cryptic habitats. Thus, the infected hosts act as "living insect bombs" against the target pest. We tested this approach using two model insect pests: a chestnut tree pest, the goat moth Cossus cossus (Lepidiptera: Cossidae), and a lawn caterpillar, Spodoptera cilium (Lepidoptera: Noctuidae). One pest is considered hard-to-reach via aqueous spray (C. cossus) and the other is more openly exposed in the environment (S. cilium). C. cossus and S. cilium studies were conducted in chestnut logs and Bermudagrass arenas, respectively. The living bomb approach was compared with standard nematode application in aqueous spray and controls (without nematode application); Steinernema carpocapsae (Rize isolate) was used in all experiments. The percentage larval mortality of C. cossus was 86% in the living insect bomb treatment, whereas, all other treatments and controls exhibited less than 4% mortality. The new approach (living bomb) was equally successful as standard aqueous application for the control of S. cilium larvae. Both methods exhibited more than 90% mortality in the turfgrass arena. Our new approach showed an immense potential to control insect pests living in hard-to-reach cryptic habitats. Copyright © 2015 Elsevier Inc. All rights reserved.

Short-rib polydactyly and Jeune syndromes are caused by mutations in WDR60.

PubMed

McInerney-Leo, Aideen M; Schmidts, Miriam; Cortés, Claudio R; Leo, Paul J; Gener, Blanca; Courtney, Andrew D; Gardiner, Brooke; Harris, Jessica A; Lu, Yeping; Marshall, Mhairi; Scambler, Peter J; Beales, Philip L; Brown, Matthew A; Zankl, Andreas; Mitchison, Hannah M; Duncan, Emma L; Wicking, Carol

2013-09-05

Short-rib polydactyly syndromes (SRPS I-V) are a group of lethal congenital disorders characterized by shortening of the ribs and long bones, polydactyly, and a range of extraskeletal phenotypes. A number of other disorders in this grouping, including Jeune and Ellis-van Creveld syndromes, have an overlapping but generally milder phenotype. Collectively, these short-rib dysplasias (with or without polydactyly) share a common underlying defect in primary cilium function and form a subset of the ciliopathy disease spectrum. By using whole-exome capture and massive parallel sequencing of DNA from an affected Australian individual with SRPS type III, we detected two novel heterozygous mutations in WDR60, a relatively uncharacterized gene. These mutations segregated appropriately in the unaffected parents and another affected family member, confirming compound heterozygosity, and both were predicted to have a damaging effect on the protein. Analysis of an additional 54 skeletal ciliopathy exomes identified compound heterozygous mutations in WDR60 in a Spanish individual with Jeune syndrome of relatively mild presentation. Of note, these two families share one novel WDR60 missense mutation, although haplotype analysis suggested no shared ancestry. We further show that WDR60 localizes at the base of the primary cilium in wild-type human chondrocytes, and analysis of fibroblasts from affected individuals revealed a defect in ciliogenesis and aberrant accumulation of the GLI2 transcription factor at the centrosome or basal body in the absence of an obvious axoneme. These findings show that WDR60 mutations can cause skeletal ciliopathies and suggest a role for WDR60 in ciliogenesis. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Regulation of polycystin-1 ciliary trafficking by motifs at its C-terminus and polycystin-2 but not by cleavage at the GPS site

PubMed Central

Su, Xuefeng; Wu, Maoqing; Yao, Gang; El-Jouni, Wassim; Luo, Chong; Tabari, Azadeh; Zhou, Jing

2015-01-01

ABSTRACT Failure to localize membrane proteins to the primary cilium causes a group of diseases collectively named ciliopathies. Polycystin-1 (PC1, also known as PKD1) is a large ciliary membrane protein defective in autosomal dominant polycystic kidney disease (ADPKD). Here, we developed a large set of PC1 expression constructs and identified multiple sequences, including a coiled-coil motif in the C-terminal tail of PC1, regulating full-length PC1 trafficking to the primary cilium. Ciliary trafficking of wild-type and mutant PC1 depends on the dose of polycystin-2 (PC2, also known as PKD2), and the formation of a PC1–PC2 complex. Modulation of the ciliary trafficking module mediated by the VxP ciliary-targeting sequence and Arf4 and Asap1 does not affect the ciliary localization of full-length PC1. PC1 also promotes PC2 ciliary trafficking. PC2 mutations truncating its C-terminal tail but not those changing the VxP sequence to AxA or impairing the pore of the channel, leading to a dead channel, affect PC1 ciliary trafficking. Cleavage at the GPCR proteolytic site (GPS) of PC1 is not required for PC1 trafficking to cilia. We propose a mutually dependent model for the ciliary trafficking of PC1 and PC2, and that PC1 ciliary trafficking is regulated by multiple cis-acting elements. As all pathogenic PC1 mutations tested here are defective in ciliary trafficking, ciliary trafficking might serve as a functional read-out for ADPKD. PMID:26430213

Regulation of polycystin-1 ciliary trafficking by motifs at its C-terminus and polycystin-2 but not by cleavage at the GPS site.

PubMed

Su, Xuefeng; Wu, Maoqing; Yao, Gang; El-Jouni, Wassim; Luo, Chong; Tabari, Azadeh; Zhou, Jing

2015-11-15

Failure to localize membrane proteins to the primary cilium causes a group of diseases collectively named ciliopathies. Polycystin-1 (PC1, also known as PKD1) is a large ciliary membrane protein defective in autosomal dominant polycystic kidney disease (ADPKD). Here, we developed a large set of PC1 expression constructs and identified multiple sequences, including a coiled-coil motif in the C-terminal tail of PC1, regulating full-length PC1 trafficking to the primary cilium. Ciliary trafficking of wild-type and mutant PC1 depends on the dose of polycystin-2 (PC2, also known as PKD2), and the formation of a PC1-PC2 complex. Modulation of the ciliary trafficking module mediated by the VxP ciliary-targeting sequence and Arf4 and Asap1 does not affect the ciliary localization of full-length PC1. PC1 also promotes PC2 ciliary trafficking. PC2 mutations truncating its C-terminal tail but not those changing the VxP sequence to AxA or impairing the pore of the channel, leading to a dead channel, affect PC1 ciliary trafficking. Cleavage at the GPCR proteolytic site (GPS) of PC1 is not required for PC1 trafficking to cilia. We propose a mutually dependent model for the ciliary trafficking of PC1 and PC2, and that PC1 ciliary trafficking is regulated by multiple cis-acting elements. As all pathogenic PC1 mutations tested here are defective in ciliary trafficking, ciliary trafficking might serve as a functional read-out for ADPKD. © 2015. Published by The Company of Biologists Ltd.

Asymmetric Distribution of Primary Cilia Allocates Satellite Cells for Self-Renewal.

PubMed

Jaafar Marican, Nur Hayati; Cruz-Migoni, Sara B; Borycki, Anne-Gaëlle

2016-06-14

Regeneration of vertebrate skeletal muscles requires satellite cells, a population of stem cells that are quiescent in normal conditions and divide, differentiate, and self-renew upon activation triggered by exercise, injury, and degenerative diseases. Satellite cell self-renewal is essential for long-term tissue homeostasis, and previous work has identified a number of external cues that control this process. However, little is known of the possible intrinsic control mechanisms of satellite cell self-renewal. Here, we show that quiescent satellite cells harbor a primary cilium, which is rapidly disassembled upon entry into the cell cycle. Contrasting with a commonly accepted belief, cilia reassembly does not occur uniformly in cells exiting the cell cycle. We found that primary cilia reassemble preferentially in cells committed to self-renew, and disruption of cilia reassembly causes a specific deficit in self-renewing satellite cells. These observations indicate that primary cilia provide an intrinsic cue essential for satellite cell self-renewal. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Kif3a Controls Murine Nephron Number Via GLI3 Repressor, Cell Survival, and Gene Expression in a Lineage-Specific Manner

PubMed Central

Chi, Lijun; Galtseva, Alevtina; Chen, Lin; Mo, Rong; Hui, Chi-chung; Rosenblum, Norman D.

2013-01-01

The primary cilium is required during early embryo patterning, epithelial tubulogenesis, and growth factor-dependent signal transduction. The requirement for primary cilia during renal epithelial-mesenchymal tissue interactions that give rise to nephrons is undefined. Here, we used Cre-mediated recombination to generate mice with Kif3a deficiency targeted to the ureteric and/or metanephric mesenchyme cell lineages in the embryonic kidney. Gradual loss of primary cilia in either lineage leads to a phenotype of reduced nephron number. Remarkably, in addition to cyst formation, loss of primary cilia in the ureteric epithelial cell leads to decreased expression of Wnt11 and Ret and reduced ureteric branching. Constitutive expression of GLI3 repressor (Gli3Δ699/+) rescues these abnormalities. In embryonic metanephric mesenchyme cells, Kif3a deficiency limits survival of nephrogenic progenitor cells and expression of genes required for nephron formation. Together, our data demonstrate that Kif3a controls nephron number via distinct cell lineage-specific mechanisms. PMID:23762375

Ciliopathies: The Trafficking Connection

PubMed Central

Madhivanan, Kayalvizhi; Aguilar, R. Claudio

2014-01-01

The primary cilium (PC) is a very dynamic hair-like membrane structure that assembles/disassembles in a cell-cycle dependent manner and is present in almost every cell type. Despite being continuous with the plasma membrane, a diffusion barrier located at the ciliary base confers the PC properties of a separate organelle with very specific characteristics and membrane composition. Therefore, vesicle trafficking is the major process by which components are acquired for cilium formation and maintenance. In fact, a system of specific sorting signals controls the right of cargo admission into the cilia. Disruption to the ciliary structure or its function leads to multi-organ diseases known as ciliopathies. These illnesses arise from a spectrum of mutations in any of the more than 50 loci linked to these conditions. Therefore, it is not surprising that symptom variability (specific manifestations and severity) among and within ciliopathies seems to be an emerging characteristic. Nevertheless, one can speculate that mutations occurring in genes whose products contribute to the overall vesicle trafficking to the PC (i.e., affecting cilia assembly) will lead to more severe symptoms, while those involved in the transport of specific cargoes will result in milder phenotypes. In this review, we summarize the trafficking mechanisms to the cilia and also provide a description of the trafficking defects observed in some ciliopathies which can be correlated to the severity of the pathology. PMID:25040720

Topography of calcium phosphate ceramics regulates primary cilia length and TGF receptor recruitment associated with osteogenesis.

PubMed

Zhang, Jingwei; Dalbay, Melis T; Luo, Xiaoman; Vrij, Erik; Barbieri, Davide; Moroni, Lorenzo; de Bruijn, Joost D; van Blitterswijk, Clemens A; Chapple, J Paul; Knight, Martin M; Yuan, Huipin

2017-07-15

The surface topography of synthetic biomaterials is known to play a role in material-driven osteogenesis. Recent studies show that TGFβ signalling also initiates osteogenic differentiation. TGFβ signalling requires the recruitment of TGFβ receptors (TGFβR) to the primary cilia. In this study, we hypothesize that the surface topography of calcium phosphate ceramics regulates stem cell morphology, primary cilia structure and TGFβR recruitment to the cilium associated with osteogenic differentiation. We developed a 2D system using two types of tricalcium phosphate (TCP) ceramic discs with identical chemistry. One sample had a surface topography at micron-scale (TCP-B, with a bigger surface structure dimension) whilst the other had a surface topography at submicron scale (TCP-S, with a smaller surface structure dimension). In the absence of osteogenic differentiation factors, human bone marrow stromal cells (hBMSCs) were more spread on TCP-S than on TCP-B with alterations in actin organization and increased primary cilia prevalence and length. The cilia elongation on TCP-S was similar to that observed on glass in the presence of osteogenic media and was followed by recruitment of transforming growth factor-β RII (p-TGFβ RII) to the cilia axoneme. This was associated with enhanced osteogenic differentiation of hBMSCs on TCP-S, as shown by alkaline phosphatase activity and gene expression for key osteogenic markers in the absence of additional osteogenic growth factors. Similarly, in vivo after a 12-week intramuscular implantation in dogs, TCP-S induced bone formation while TCP-B did not. It is most likely that the surface topography of calcium phosphate ceramics regulates primary cilia length and ciliary recruitment of p-TGFβ RII associated with osteogenesis and bone formation. This bioengineering control of osteogenesis via primary cilia modulation may represent a new type of biomaterial-based ciliotherapy for orthopedic, dental and maxillofacial surgery applications. The surface topography of synthetic biomaterials plays important roles in material-driven osteogenesis. The data presented herein have shown that the surface topography of calcium phosphate ceramics regulates mesenchymal stromal cells (e.g., human bone marrow mesenchymal stromal cells, hBMSCs) with respect to morphology, primary cilia structure and TGFβR recruitment to the cilium associated with osteogenic differentiation in vitro. Together with bone formation in vivo, our results suggested a new type of biomaterial-based ciliotherapy for orthopedic, dental and maxillofacial surgery by the bioengineering control of osteogenesis via primary cilia modulation. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Prostaglandin signalling regulates ciliogenesis by modulating intraflagellar transport.

PubMed

Jin, Daqing; Ni, Terri T; Sun, Jianjian; Wan, Haiyan; Amack, Jeffrey D; Yu, Guangju; Fleming, Jonathan; Chiang, Chin; Li, Wenyan; Papierniak, Anna; Cheepala, Satish; Conseil, Gwenaëlle; Cole, Susan P C; Zhou, Bin; Drummond, Iain A; Schuetz, John D; Malicki, Jarema; Zhong, Tao P

2014-09-01

Cilia are microtubule-based organelles that mediate signal transduction in a variety of tissues. Despite their importance, the signalling cascades that regulate cilium formation remain incompletely understood. Here we report that prostaglandin signalling affects ciliogenesis by regulating anterograde intraflagellar transport (IFT). Zebrafish leakytail (lkt) mutants show ciliogenesis defects, and the lkt locus encodes an ATP-binding cassette transporter (ABCC4). We show that Lkt/ABCC4 localizes to the cell membrane and exports prostaglandin E2 (PGE2), a function that is abrogated by the Lkt/ABCC4(T804M) mutant. PGE2 synthesis enzyme cyclooxygenase-1 and its receptor, EP4, which localizes to the cilium and activates the cyclic-AMP-mediated signalling cascade, are required for cilium formation and elongation. Importantly, PGE2 signalling increases anterograde but not retrograde velocity of IFT and promotes ciliogenesis in mammalian cells. These findings lead us to propose that Lkt/ABCC4-mediated PGE2 signalling acts through a ciliary G-protein-coupled receptor, EP4, to upregulate cAMP synthesis and increase anterograde IFT, thereby promoting ciliogenesis.

IFT trains in different stages of assembly queue at the ciliary base for consecutive release into the cilium

PubMed Central

Wingfield, Jenna L; Mengoni, Ilaria; Bomberger, Heather; Jiang, Yu-Yang; Walsh, Jonathon D; Brown, Jason M; Picariello, Tyler; Cochran, Deborah A; Zhu, Bing; Pan, Junmin; Eggenschwiler, Jonathan; Gaertig, Jacek; Witman, George B; Kner, Peter; Lechtreck, Karl

2017-01-01

Intraflagellar transport (IFT) trains, multimegadalton assemblies of IFT proteins and motors, traffic proteins in cilia. To study how trains assemble, we employed fluorescence protein-tagged IFT proteins in Chlamydomonas reinhardtii. IFT-A and motor proteins are recruited from the cell body to the basal body pool, assembled into trains, move through the cilium, and disperse back into the cell body. In contrast to this ‘open’ system, IFT-B proteins from retrograde trains reenter the pool and a portion is reused directly in anterograde trains indicating a ‘semi-open’ system. Similar IFT systems were also observed in Tetrahymena thermophila and IMCD3 cells. FRAP analysis indicated that IFT proteins and motors of a given train are sequentially recruited to the basal bodies. IFT dynein and tubulin cargoes are loaded briefly before the trains depart. We conclude that the pool contains IFT trains in multiple stages of assembly queuing for successive release into the cilium upon completion. DOI: http://dx.doi.org/10.7554/eLife.26609.001 PMID:28562242

Kin5 Knockdown in Tetrahymena thermophila Using RNAi Blocks Cargo Transport of Gef1

PubMed Central

Awan, Aashir; Bell, Aaron J.; Satir, Peter

2009-01-01

A critical process that builds and maintains the eukaryotic cilium is intraflagellar transport (IFT). This process utilizes members of the kinesin-2 superfamily to transport cargo into the cilium (anterograde transport) and a dynein motor for the retrograde traffic. Using a novel RNAi knockdown method, we have analyzed the function of the homodimeric IFT kinesin-2, Kin5, in Tetrahymena ciliary transport. In RNAi transformants, Kin5 was severely downregulated and disappeared from the cilia, but cilia did not resorb, although tip structure was affected. After deciliation of the knockdown cell, cilia regrew and cells swam, which suggested that Kin5 is not responsible for the trafficking of axonemal precursors to build the cilium, but could be transporting molecules that act in ciliary signal transduction, such as guanine nucleotide exchange proteins (GEFs). Gef1 is a Tetrahymena ciliary protein, and current coimmunoprecipitation and immunofluorescence studies showed that it is absent in regrowing cilia of the knockdown cells lacking ciliary Kin5. We suggest that one important cargo of Kin5 is Gef1 and knockdown of Kin5 results in cell lethality. PMID:19290045

Chemically-inducible diffusion trap at cilia (C-IDTc) reveals molecular sieve-like barrier

PubMed Central

Lin, Yu-Chun; Phua, Siew Cheng; Jiao, John; Levchenko, Andre; Inoue, Takafumi; Rohatgi, Rajat; Inoue, Takanari

2013-01-01

Primary cilia function as specialized compartments for signal transduction. The stereotyped structure and signaling function of cilia inextricably depend on the selective segregation of molecules in cilia. However, the fundamental principles governing the access of soluble proteins to primary cilia remain unresolved. We developed a methodology termed Chemically-Inducible Diffusion Trap at Cilia (C-IDTc) to visualize the diffusion process of a series of fluorescent proteins ranging in size from 3.2 to 7.9 nm into primary cilia. We found that the interior of the cilium was accessible to proteins as large as 7.9 nm. The kinetics of ciliary accumulation of this panel of proteins was exponentially limited by their Stokes radii. Quantitative modeling suggests that the diffusion barrier operates as a molecular sieve at the base of cilia. Our study presents a set of powerful, generally applicable tools for the quantitative monitoring of ciliary protein diffusion under both physiological and pathological conditions. PMID:23666116

Spatial distribution of calcium-gated chloride channels in olfactory cilia.

PubMed

French, Donald A; Badamdorj, Dorjsuren; Kleene, Steven J

2010-12-30

In vertebrate olfactory receptor neurons, sensory cilia transduce odor stimuli into changes in neuronal membrane potential. The voltage changes are primarily caused by the sequential openings of two types of channel: a cyclic-nucleotide-gated (CNG) cationic channel and a calcium-gated chloride channel. In frog, the cilia are 25 to 200 µm in length, so the spatial distributions of the channels may be an important determinant of odor sensitivity. To determine the spatial distribution of the chloride channels, we recorded from single cilia as calcium was allowed to diffuse down the length of the cilium and activate the channels. A computational model of this experiment allowed an estimate of the spatial distribution of the chloride channels. On average, the channels were concentrated in a narrow band centered at a distance of 29% of the ciliary length, measured from the base of the cilium. This matches the location of the CNG channels determined previously. This non-uniform distribution of transduction proteins is consistent with similar findings in other cilia. On average, the two types of olfactory transduction channel are concentrated in the same region of the cilium. This may contribute to the efficient detection of weak stimuli.

"Lollipop-shaped" high-sensitivity Microelectromechanical Systems vector hydrophone based on Parylene encapsulation

NASA Astrophysics Data System (ADS)

Liu, Yuan; Wang, Renxin; Zhang, Guojun; Du, Jin; Zhao, Long; Xue, Chenyang; Zhang, Wendong; Liu, Jun

2015-07-01

This paper presents methods of promoting the sensitivity of Microelectromechanical Systems (MEMS) vector hydrophone by increasing the sensing area of cilium and perfect insulative Parylene membrane. First, a low-density sphere is integrated with the cilium to compose a "lollipop shape," which can considerably increase the sensing area. A mathematic model on the sensitivity of the "lollipop-shaped" MEMS vector hydrophone is presented, and the influences of different structural parameters on the sensitivity are analyzed via simulation. Second, the MEMS vector hydrophone is encapsulated through the conformal deposition of insulative Parylene membrane, which enables underwater acoustic monitoring without any typed sound-transparent encapsulation. Finally, the characterization results demonstrate that the sensitivity reaches up to -183 dB (500 Hz 0dB at 1 V/ μPa ), which is increased by more than 10 dB, comparing with the previous cilium-shaped MEMS vector hydrophone. Besides, the frequency response takes on a sensitivity increment of 6 dB per octave. The working frequency band is 20-500 Hz and the concave point depth of 8-shaped directivity is beyond 30 dB, indicating that the hydrophone is promising in underwater acoustic application.

Production and characterization of human induced pluripotent stem cells (iPSCs) from Joubert Syndrome: CSSi001-A (2850).

PubMed

Rosati, Jessica; Altieri, Filomena; Tardivo, Silvia; Turco, Elisa Maria; Goldoni, Marina; Spasari, Iolanda; Ferrari, Daniela; Bernardini, Laura; Lamorte, Giuseppe; Valente, Enza Maria; Vescovi, Angelo Luigi

2018-03-01

Joubert Syndrome (JS) is a rare autosomal recessive or X-linked condition characterized by a peculiar cerebellar malformation, known as the molar tooth sign (MTS), associated with other neurological phenotypes and multiorgan involvement. JS is a ciliopathy, a spectrum of disorders whose causative genes encode proteins involved in the primary cilium apparatus. In order to elucidate ciliopathy-associated molecular mechanisms, human induced pluripotent stem cells (hiPSCs) were derived from a patient affected by JS carrying a homozygous missense mutation in the AHI1 gene (p.H896R) that encodes a protein named Jouberin. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Polarized Ends of Human Macula Densa Cells: Ultrastructural Investigation and Morphofunctional Correlations.

PubMed

Cangiotti, Angela Maria; Lorenzi, Teresa; Zingaretti, Maria Cristina; Fabri, Mara; Morroni, Manrico

2018-05-01

The morphology of the kidney macula densa (MD) has extensively been investigated in animals, whereas human studies are scanty. We studied the fine structure of human MD cells focusing on their apical and basal ends and correlating structure and function. The MD region was examined by transmission electron microscopy in six renal biopsies from patients with kidney disease. Ultrastructural analysis of MD cells was performed on serial sections. MD cells show two polarized ends. The apical portion is characterized by a single, immotile cilium associated with microvilli; apically, cells are joined by adhering junctions. In the basal portion, the cytoplasm contains small, dense granules and numerous, irregular cytoplasmic projections extending to the adjacent extraglomerular mesangium. The projections often contain small, dense granules. A reticulated basement membrane around MD cells separates them from the extraglomerular mesangium. Although the fact that tissue specimens came from patients with kidney disease mandates extreme caution, ultrastructural examination confirmed that MD cells have sensory features due to the presence of the primary cilium, that they are connected by apical adhering junctions forming a barrier that separates the tubular flow from the interstitium, and that they present numerous basal interdigitations surrounded by a reticulated basement membrane. Conceivably, the latter two features are related to the functional activity of the MD. The small, dense granules in the basal cytoplasm and in cytoplasmic projections are likely related to the paracrine function of MD cells. Anat Rec, 301:922-931, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

GLIS1-3 transcription factors: critical roles in the regulation of multiple physiological processes and diseases.

PubMed

Jetten, Anton M

2018-05-19

Krüppel-like zinc finger proteins form one of the largest families of transcription factors. They function as key regulators of embryonic development and a wide range of other physiological processes, and are implicated in a variety of pathologies. GLI-similar 1-3 (GLIS1-3) constitute a subfamily of Krüppel-like zinc finger proteins that act either as activators or repressors of gene transcription. GLIS3 plays a critical role in the regulation of multiple biological processes and is a key regulator of pancreatic β cell generation and maturation, insulin gene expression, thyroid hormone biosynthesis, spermatogenesis, and the maintenance of normal kidney functions. Loss of GLIS3 function in humans and mice leads to the development of several pathologies, including neonatal diabetes and congenital hypothyroidism, polycystic kidney disease, and infertility. Single nucleotide polymorphisms in GLIS3 genes have been associated with increased risk of several diseases, including type 1 and type 2 diabetes, glaucoma, and neurological disorders. GLIS2 plays a critical role in the kidney and GLIS2 dysfunction leads to nephronophthisis, an end-stage, cystic renal disease. In addition, GLIS1-3 have regulatory functions in several stem/progenitor cell populations. GLIS1 and GLIS3 greatly enhance reprogramming efficiency of somatic cells into induced embryonic stem cells, while GLIS2 inhibits reprogramming. Recent studies have obtained substantial mechanistic insights into several physiological processes regulated by GLIS2 and GLIS3, while a little is still known about the physiological functions of GLIS1. The localization of some GLIS proteins to the primary cilium suggests that their activity may be regulated by a downstream primary cilium-associated signaling pathway. Insights into the upstream GLIS signaling pathway may provide opportunities for the development of new therapeutic strategies for diabetes, hypothyroidism, and other diseases.

Primary Cilia Are Not Calcium-Responsive Mechanosensors

PubMed Central

Delling, M.; Indzhykulian, A. A.; Liu, X.; Liu, Y.; Xie, T.; Corey, D. P.; Clapham, D. E.

2016-01-01

Primary cilia are solitary, generally non-motile, hair-like protrusions that extend from the surface of cells between cell divisions. Their antenna-like structure leads naturally to the assumption that they sense the surrounding environment, the most common hypothesis being sensation of mechanical force through calcium-permeable ion channels within the cilium1. This Ca2+- Responsive MechanoSensor (CaRMS) hypothesis for primary cilia has been invoked to explain a large range of biological responses, from control of left-right axis determination in embryonic development to adult progression of polycystic kidney disease and some cancers2,3. Here, we report the complete lack of mechanically induced calcium increases in primary cilia, in tissues upon which this hypothesis has been based. First, we developed a transgenic mouse, Arl13b-mCherry-GECO1.2, expressing a ratiometric genetically encoded calcium indicator (GECI) in all primary cilia. We then measured responses to flow in primary cilia of cultured kidney epithelial cells, kidney thick ascending tubules, crown cells of the embryonic node, kinocilia of inner ear hair cells, and several cell lines. Cilia-specific Ca2+ influxes were not observed in physiological or even highly supraphysiological levels of fluid flow. We conclude that mechanosensation, if it originates in primary cilia, is not via calcium signaling. PMID:27007841

Increased Na+/H+ exchanger activity on the apical surface of a cilium-deficient cortical collecting duct principal cell model of polycystic kidney disease

PubMed Central

Olteanu, Dragos; Liu, Xiaofen; Liu, Wen; Roper, Venus C.; Sharma, Neeraj; Yoder, Bradley K.; Satlin, Lisa M.; Schwiebert, Erik M.

2012-01-01

Pathophysiological anomalies in autosomal dominant and recessive forms of polycystic kidney disease (PKD) may derive from impaired function/formation of the apical central monocilium of ductal epithelia such as that seen in the Oak Ridge polycystic kidney or orpk (Ift88Tg737Rpw) mouse and its immortalized cell models for the renal collecting duct. According to a previous study, Na/H exchanger (NHE) activity may contribute to hyperabsorptive Na+ movement in cilium-deficient (“mutant”) cortical collecting duct principal cell monolayers derived from the orpk mice compared with cilium-competent (“rescued”) monolayers. To examine NHE activity, we measured intracellular pH (pHi) by fluorescence imaging with the pH-sensitive dye BCECF, and used a custom-designed perfusion chamber to control the apical and basolateral solutions independently. Both mutant and rescued monolayers exhibited basolateral Na+-dependent acid-base transporter activity in the nominal absence of CO2/HCO3−. However, only the mutant cells displayed appreciable apical Na+-induced pHi recoveries from NH4+ prepulse-induced acid loads. Similar results were obtained with isolated, perfused collecting ducts from orpk vs. wild-type mice. The pHi dependence of basolateral cariporide/HOE-694-sensitive NHE activity under our experimental conditions was similar in both mutant and rescued cells, and 3.5- to 4.5-fold greater than apical HOE-sensitive NHE activity in the mutant cells (pHi 6.23–6.68). Increased apical NHE activity correlated with increased apical NHE1 expression in the mutant cells, and increased apical localization in collecting ducts of kidney sections from orpk vs. control mice. A kidney-specific conditional cilium-knockout mouse produced a more acidic urine compared with wild-type littermates and became alkalotic by 28 days of age. This study provides the first description of altered NHE activity, and an associated acid-base anomaly in any form of PKD. PMID:22301060

Mutations in ARL2BP, Encoding ADP-Ribosylation-Factor-Like 2 Binding Protein, Cause Autosomal-Recessive Retinitis Pigmentosa

PubMed Central

Davidson, Alice E.; Schwarz, Nele; Zelinger, Lina; Stern-Schneider, Gabriele; Shoemark, Amelia; Spitzbarth, Benjamin; Gross, Menachem; Laxer, Uri; Sosna, Jacob; Sergouniotis, Panagiotis I.; Waseem, Naushin H.; Wilson, Robert; Kahn, Richard A.; Plagnol, Vincent; Wolfrum, Uwe; Banin, Eyal; Hardcastle, Alison J.; Cheetham, Michael E.; Sharon, Dror; Webster, Andrew R.

2013-01-01

Retinitis pigmentosa (RP) is a genetically heterogeneous retinal degeneration characterized by photoreceptor death, which results in visual failure. Here, we used a combination of homozygosity mapping and exome sequencing to identify mutations in ARL2BP, which encodes an effector protein of the small GTPases ARL2 and ARL3, as causative for autosomal-recessive RP (RP66). In a family affected by RP and situs inversus, a homozygous, splice-acceptor mutation, c.101−1G>C, which alters pre-mRNA splicing of ARLBP2 in blood RNA, was identified. In another family, a homozygous c.134T>G (p.Met45Arg) mutation was identified. In the mouse retina, ARL2BP localized to the basal body and cilium-associated centriole of photoreceptors and the periciliary extension of the inner segment. Depletion of ARL2BP caused cilia shortening. Moreover, depletion of ARL2, but not ARL3, caused displacement of ARL2BP from the basal body, suggesting that ARL2 is vital for recruiting or anchoring ARL2BP at the base of the cilium. This hypothesis is supported by the finding that the p.Met45Arg amino acid substitution reduced binding to ARL2 and caused the loss of ARL2BP localization at the basal body in ciliated nasal epithelial cells. These data demonstrate a role for ARL2BP and ARL2 in primary cilia function and that this role is essential for normal photoreceptor maintenance and function. PMID:23849777

Low-intensity pulsed ultrasound stimulation promotes osteoblast differentiation through hedgehog signaling.

PubMed

Matsumoto, Kenichi; Shimo, Tsuyoshi; Kurio, Naito; Okui, Tatsuo; Ibaragi, Soichiro; Kunisada, Yuki; Obata, Kyoichi; Masui, Masanori; Pai, Pang; Horikiri, Yuu; Yamanaka, Nobuyuki; Takigawa, Masaharu; Sasaki, Akira

2018-06-01

Low-intensity pulsed ultrasound (LIPUS) has been used as an adjunct to fracture healing therapies, but the mechanisms underlying its action are not known. We reported that sonic hedgehog (SHH) signaling was activated in osteoblasts at the dynamic remodeling site of a bone fracture. Mechanical stimulation is a crucial factor in bone remodeling, and it is related to the primary cilia as a sensor of hedgehog signaling. Here we observed that LIPUS promoted callus formation in accord with Gli2-positive cells after 14 days at the mouse femur fractured site compared with a control group. An immunofluorescence analysis showed that the numbers of primary cilia and cilia/osterix double-positive osteoblasts were increased at the fracture site by LIPUS. LIPUS stimulated not only the number and the length of primary cilia, but also the levels of ciliated protein, Ift88 mRNA, and SHH, Gli1, and Gli2 in MC3T3-E1 cells. Further experiments revealed that LIPUS stimulated osteogenic differentiation in the presence of smoothened agonist (SAG) treatment. These results indicate that LIPUS stimulates osteogenic differentiation and the maturation of osteoblasts by a primary cilium-mediated activation of hedgehog signaling. © 2017 Wiley Periodicals, Inc.

Ndel1 suppresses ciliogenesis in proliferating cells by regulating the trichoplein-Aurora A pathway.

PubMed

Inaba, Hironori; Goto, Hidemasa; Kasahara, Kousuke; Kumamoto, Kanako; Yonemura, Shigenobu; Inoko, Akihito; Yamano, Shotaro; Wanibuchi, Hideki; He, Dongwei; Goshima, Naoki; Kiyono, Tohru; Hirotsune, Shinji; Inagaki, Masaki

2016-02-15

Primary cilia protrude from the surface of quiescent cells and disassemble at cell cycle reentry. We previously showed that ciliary reassembly is suppressed by trichoplein-mediated Aurora A activation pathway in growing cells. Here, we report that Ndel1, a well-known modulator of dynein activity, localizes at the subdistal appendage of the mother centriole, which nucleates a primary cilium. In the presence of serum, Ndel1 depletion reduces trichoplein at the mother centriole and induces unscheduled primary cilia formation, which is reverted by forced trichoplein expression or coknockdown of KCTD17 (an E3 ligase component protein for trichoplein). Serum starvation induced transient Ndel1 degradation, subsequent to the disappearance of trichoplein at the mother centriole. Forced expression of Ndel1 suppressed trichoplein degradation and axonemal microtubule extension during ciliogenesis, similar to trichoplein induction or KCTD17 knockdown. Most importantly, the proportion of ciliated and quiescent cells was increased in the kidney tubular epithelia of newborn Ndel1-hypomorphic mice. Thus, Ndel1 acts as a novel upstream regulator of the trichoplein-Aurora A pathway to inhibit primary cilia assembly. © 2016 Inaba et al.

Distinct functions for IFT140 and IFT20 in opsin transport.

PubMed Central

Crouse, Jacquelin A.; Lopes, Vanda S.; SanAgustin, Jovenal T.; Keady, Brian T.; Williams, David S.; Pazour, Gregory J.

2014-01-01

In the vertebrate retina, light is detected by the outer segments of photoreceptor rods and cones, which are highly modified cilia. Like other cilia, outer segments have no protein synthetic capacity and depend on proteins made in the cell body for their formation and maintenance. The mechanism of transport into the outer segment is not fully understood but intraflagellar transport (IFT) is thought to be a major mechanism for moving protein from the cell body into the cilium. In the case of photoreceptor cells, the high density of receptors and the disk turnover that occurs daily necessitates much higher rates of transport than would be required in other cilia. In this work, we show that the IFT complex A protein IFT140 is required for development and maintenance of outer segments. In earlier work we found that acute deletion of Ift20 caused opsin to accumulate at the Golgi complex. In this work we find that acute deletion of Ift140 does not cause opsin to accumulate at the Golgi complex but rather it accumulates in the plasma membrane of the inner segments. This work is strong support of a model of opsin transport where IFT20 is involved in the movement from the Golgi complex to the base of the cilium. Then, once at the base, the opsin is carried through the connecting cilium by an IFT complex that includes IFT140. PMID:24619649

BLOC-1 is required for selective membrane protein trafficking from endosomes to primary cilia

PubMed Central

2017-01-01

Primary cilia perceive the extracellular environment through receptors localized in the ciliary membrane, but mechanisms directing specific proteins to this domain are poorly understood. To address this question, we knocked down proteins potentially important for ciliary membrane targeting and determined how this affects the ciliary trafficking of fibrocystin, polycystin-2, and smoothened. Our analysis showed that fibrocystin and polycystin-2 are dependent on IFT20, GMAP210, and the exocyst complex, while smoothened delivery is largely independent of these components. In addition, we found that polycystin-2, but not smoothened or fibrocystin, requires the biogenesis of lysosome-related organelles complex-1 (BLOC-1) for ciliary delivery. Consistent with the role of BLOC-1 in sorting from the endosome, we find that disrupting the recycling endosome reduces ciliary polycystin-2 and causes its accumulation in the recycling endosome. This is the first demonstration of a role for BLOC-1 in ciliary assembly and highlights the complexity of pathways taken to the cilium. PMID:28576874

Protein sorting, targeting and trafficking in photoreceptor cells

PubMed Central

Pearring, Jillian N.; Salinas, Raquel Y.; Baker, Sheila A.; Arshavsky, Vadim Y.

2013-01-01

Vision is the most fundamental of our senses initiated when photons are absorbed by the rod and cone photoreceptor neurons of the retina. At the distal end of each photoreceptor resides a light-sensing organelle, called the outer segment, which is a modified primary cilium highly enriched with proteins involved in visual signal transduction. At the proximal end, each photoreceptor has a synaptic terminal, which connects this cell to the downstream neurons for further processing of the visual information. Understanding the mechanisms involved in creating and maintaining functional compartmentalization of photoreceptor cells remains among the most fascinating topics in ocular cell biology. This review will discuss how photoreceptor compartmentalization is supported by protein sorting, targeting and trafficking, with an emphasis on the best-studied cases of outer segment-resident proteins. PMID:23562855

Ccdc11 is a novel centriolar satellite protein essential for ciliogenesis and establishment of left-right asymmetry.

PubMed

Silva, Erica; Betleja, Ewelina; John, Emily; Spear, Philip; Moresco, James J; Zhang, Siwei; Yates, John R; Mitchell, Brian J; Mahjoub, Moe R

2016-01-01

The establishment of left-right (L-R) asymmetry in vertebrates is dependent on the sensory and motile functions of cilia during embryogenesis. Mutations in CCDC11 disrupt L-R asymmetry and cause congenital heart disease in humans, yet the molecular and cellular functions of the protein remain unknown. Here we demonstrate that Ccdc11 is a novel component of centriolar satellites-cytoplasmic granules that serve as recruitment sites for proteins destined for the centrosome and cilium. Ccdc11 interacts with core components of satellites, and its loss disrupts the subcellular organization of satellite proteins and perturbs primary cilium assembly. Ccdc11 colocalizes with satellite proteins in human multiciliated tracheal epithelia, and its loss inhibits motile ciliogenesis. Similarly, depletion of CCDC11 in Xenopus embryos causes defective assembly and motility of cilia in multiciliated epidermal cells. To determine the role of CCDC11 during vertebrate development, we generated mutant alleles in zebrafish. Loss of CCDC11 leads to defective ciliogenesis in the pronephros and within the Kupffer's vesicle and results in aberrant L-R axis determination. Our results highlight a critical role for Ccdc11 in the assembly and function of motile cilia and implicate centriolar satellite-associated proteins as a new class of proteins in the pathology of L-R patterning and congenital heart disease. © 2016 Silva, Betleja, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Mathematical embryology: the fluid mechanics of nodal cilia

NASA Astrophysics Data System (ADS)

Smith, D. J.; Smith, A. A.; Blake, J. R.

2011-07-01

Left-right symmetry breaking is critical to vertebrate embryonic development; in many species this process begins with cilia-driven flow in a structure termed the `node'. Primary `whirling' cilia, tilted towards the posterior, transport morphogen-containing vesicles towards the left, initiating left-right asymmetric development. We review recent theoretical models based on the point-force stokeslet and point-torque rotlet singularities, explaining how rotation and surface-tilt produce directional flow. Analysis of image singularity systems enforcing the no-slip condition shows how tilted rotation produces a far-field `stresslet' directional flow, and how time-dependent point-force and time-independent point-torque models are in this respect equivalent. Associated slender body theory analysis is reviewed; this approach enables efficient and accurate simulation of three-dimensional time-dependent flow, time-dependence being essential in predicting features of the flow such as chaotic advection, which have subsequently been determined experimentally. A new model for the nodal flow utilising the regularized stokeslet method is developed, to model the effect of the overlying Reichert's membrane. Velocity fields and particle paths within the enclosed domain are computed and compared with the flow profiles predicted by previous `membrane-less' models. Computations confirm that the presence of the membrane produces flow-reversal in the upper region, but no continuous region of reverse flow close to the epithelium. The stresslet far-field is no longer evident in the membrane model, due to the depth of the cavity being of similar magnitude to the cilium length. Simulations predict that vesicles released within one cilium length of the epithelium are generally transported to the left via a `loopy drift' motion, sometimes involving highly unpredictable detours around leftward cilia [truncated

Protein Interaction Analysis Provides a Map of the Spatial and Temporal Organization of the Ciliary Gating Zone.

PubMed

Takao, Daisuke; Wang, Liang; Boss, Allison; Verhey, Kristen J

2017-08-07

The motility and signaling functions of the primary cilium require a unique protein and lipid composition that is determined by gating mechanisms localized at the base of the cilium. Several protein complexes localize to the gating zone and may regulate ciliary protein composition; however, the mechanisms of ciliary gating and the dynamics of the gating components are largely unknown. Here, we used the BiFC (bimolecular fluorescence complementation) assay and report for the first time on the protein-protein interactions that occur between ciliary gating components and transiting cargoes during ciliary entry. We find that the nucleoporin Nup62 and the C termini of the nephronophthisis (NPHP) proteins NPHP4 and NPHP5 interact with the axoneme-associated kinesin-2 motor KIF17 and thus spatially map to the inner region of the ciliary gating zone. Nup62 and NPHP4 exhibit rapid turnover at the transition zone and thus define dynamic components of the gate. We find that B9D1, AHI1, and the N termini of NPHP4 and NPHP5 interact with the transmembrane protein SSTR3 and thus spatially map to the outer region of the ciliary gating zone. B9D1, AHI1, and NPHP5 exhibit little to no turnover at the transition zone and thus define components of a stable gating structure. These data provide the first comprehensive map of the molecular orientations of gating zone components along the inner-to-outer axis of the ciliary gating zone. These results advance our understanding of the functional roles of gating zone components in regulating ciliary protein composition. Copyright © 2017 Elsevier Ltd. All rights reserved.

Super-Resolution Imaging Reveals TCTN2 Depletion-Induced IFT88 Lumen Leakage and Ciliary Weakening.

PubMed

Weng, Rueyhung Roc; Yang, T Tony; Huang, Chia-En; Chang, Chih-Wei; Wang, Won-Jing; Liao, Jung-Chi

2018-06-01

The primary cilium is an essential organelle mediating key signaling activities, such as sonic hedgehog signaling. The molecular composition of the ciliary compartment is distinct from that of the cytosol, with the transition zone (TZ) gated the ciliary base. The TZ is a packed and organized protein complex containing multiple ciliopathy-associated protein species. Tectonic 2 (TCTN2) is one of the TZ proteins in the vicinity of the ciliary membrane, and its mutation is associated with Meckel syndrome. Despite its importance in ciliopathies, the role of TCTN2 in ciliary structure and molecules remains unclear. Here, we created a CRISPR/Cas9 TCTN2 knockout human retinal pigment epithelial cell line and conducted quantitative analysis of geometric localization using both wide-field and super-resolution microscopy techniques. We found that TCTN2 depletion resulted in partial TZ damage, loss of ciliary membrane proteins, leakage of intraflagellar transport protein IFT88 toward the basal body lumen, and cilium shortening and curving. The basal body lumen occupancy of IFT88 was also observed in si-RPGRIP1L cells and cytochalasin-D-treated wild-type cells, suggesting varying lumen accessibility for intraflagellar transport proteins under different perturbed conditions. Our findings support two possible models for the lumen leakage of IFT88, i.e., a tip leakage model and a misregulation model. Together, our quantitative image analysis augmented by super-resolution microscopy facilitates the observation of structural destruction and molecular redistribution in TCTN2 -/- cilia, shedding light on mechanistic understanding of TZ-protein-associated ciliopathies. Copyright © 2018 Biophysical Society. Published by Elsevier Inc. All rights reserved.

CC2D2A Is Mutated in Joubert Syndrome and Interacts with the Ciliopathy-Associated Basal Body Protein CEP290

PubMed Central

Gorden, Nicholas T.; Arts, Heleen H.; Parisi, Melissa A.; Coene, Karlien L.M.; Letteboer, Stef J.F.; van Beersum, Sylvia E.C.; Mans, Dorus A.; Hikida, Abigail; Eckert, Melissa; Knutzen, Dana; Alswaid, Abdulrahman F.; Özyurek, Hamit; Dibooglu, Sel; Otto, Edgar A.; Liu, Yangfan; Davis, Erica E.; Hutter, Carolyn M.; Bammler, Theo K.; Farin, Frederico M.; Dorschner, Michael; Topçu, Meral; Zackai, Elaine H.; Rosenthal, Phillip; Owens, Kelly N.; Katsanis, Nicholas; Vincent, John B.; Hildebrandt, Friedhelm; Rubel, Edwin W.; Raible, David W.; Knoers, Nine V.A.M.; Chance, Phillip F.; Roepman, Ronald; Moens, Cecilia B.; Glass, Ian A.; Doherty, Dan

2008-01-01

Joubert syndrome and related disorders (JSRD) are primarily autosomal-recessive conditions characterized by hypotonia, ataxia, abnormal eye movements, and intellectual disability with a distinctive mid-hindbrain malformation. Variable features include retinal dystrophy, cystic kidney disease, and liver fibrosis. JSRD are included in the rapidly expanding group of disorders called ciliopathies, because all six gene products implicated in JSRD (NPHP1, AHI1, CEP290, RPGRIP1L, TMEM67, and ARL13B) function in the primary cilium/basal body organelle. By using homozygosity mapping in consanguineous families, we identify loss-of-function mutations in CC2D2A in JSRD patients with and without retinal, kidney, and liver disease. CC2D2A is expressed in all fetal and adult tissues tested. In ciliated cells, we observe localization of recombinant CC2D2A at the basal body and colocalization with CEP290, whose cognate gene is mutated in multiple hereditary ciliopathies. In addition, the proteins can physically interact in vitro, as shown by yeast two-hybrid and GST pull-down experiments. A nonsense mutation in the zebrafish CC2D2A ortholog (sentinel) results in pronephric cysts, a hallmark of ciliary dysfunction analogous to human cystic kidney disease. Knockdown of cep290 function in sentinel fish results in a synergistic pronephric cyst phenotype, revealing a genetic interaction between CC2D2A and CEP290 and implicating CC2D2A in cilium/basal body function. These observations extend the genetic spectrum of JSRD and provide a model system for studying extragenic modifiers in JSRD and other ciliopathies. PMID:18950740

Characterization of primary cilia in human airway smooth muscle cells.

PubMed

Wu, Jun; Du, Hui; Wang, Xiangling; Mei, Changlin; Sieck, Gary C; Qian, Qi

2009-08-01

Considerable evidence indicates a key role for primary cilia of mammalian cells in mechanochemical sensing. Dysfunctions of primary cilia have been linked to the pathogenesis of several human diseases. However, cilia-related research has been limited to a few cell and tissue types; to our knowledge, no literature exists on primary cilia in airway smooth muscle (ASM). The aim of this study was to characterize primary cilia in human ASM. Primary cilia of human bronchial smooth muscle cells (HBSMCs) were examined using immunofluorescence confocal microscopy, and scanning and transmission electron microscopy. HBSMC migration and injury repair were examined by scratch-wound and epidermal growth factor (EGF)-induced migration assays. Cross-sectional images of normal human bronchi revealed that primary cilia of HBSMCs within each ASM bundle aggregated at the same horizontal level, forming a "cilium layer." Individual cilia of HBSMCs projected into extracellular matrix and exhibited varying degrees of deflection. Mechanochemical sensing molecules, polycystins, and alpha2-, alpha5-, and beta1-integrins were enriched in cilia, as was EGF receptor, known to activate jointly with integrins during cell migration. Migration assays demonstrated a ciliary contribution to HBSMC migration and wound repair. The primary cilia of ASM cells exert a role in sensing and transducing extracellular mechanochemical signals and in ASM injury repair. Defects in ASM ciliary function could potentially affect airway wall maintenance and/or remodeling, possibly relating to the genesis of bronchiectasis in autosomal dominant polycystic kidney disease, a disease of ciliopathy.

Ciliary behavior of a negatively phototactic Chlamydomonas reinhardtii.

PubMed

Josef, Keith; Saranak, Jureepan; Foster, Kenneth W

2005-06-01

With an instrument that can record the motion of both cilia of the unicellular alga Chlamydomonas reinhardtii for many hours, the behavioral differences of its two cilia have been studied to determine their specific role in phototaxis. The organism was held on a fixed micropipette with the plane of ciliary beating rotated into the imaging plane of a quadrant photodetector. The responses to square-wave light patterns of a wide range of temporal frequencies were used to characterize the responses of each cilium. Eighty-one cells were examined showing an unexpectedly diverse range of responses. Plausible common signals for the linear and nonlinear signals from the cell body are suggested. Three independent ciliary measures--the beat frequency, stroke velocity, and phasing of the two cilia--have been identified. The cell body communicates to the cilia the direction of phototaxis the cell desires to go, the absolute light intensity, and the appropriate graded transient response for tracking the light source. The complexity revealed by each measure of the ciliary response indicates many independent variables are involved in the net phototactic response. In spite of their morphological similarity, the two cilia of Chlamydomonas respond uniquely. Probably the signals from the cell body fan out to independent pathways in the cilia. Each cilium modifies the input in its own way. The change in the pattern of the effective and recovery strokes of each cilium associated with negative phototaxis has been demonstrated and its involvement in phototactic turning is described. Copyright (c) 2005 Wiley-Liss, Inc.

Three-dimensional organization of nascent rod outer segment disk membranes.

PubMed

Volland, Stefanie; Hughes, Louise C; Kong, Christina; Burgess, Barry L; Linberg, Kenneth A; Luna, Gabriel; Zhou, Z Hong; Fisher, Steven K; Williams, David S

2015-12-01

The vertebrate photoreceptor cell contains an elaborate cilium that includes a stack of phototransductive membrane disks. The disk membranes are continually renewed, but how new disks are formed remains poorly understood. Here we used electron microscope tomography to obtain 3D visualization of the nascent disks of rod photoreceptors in three mammalian species, to gain insight into the process of disk morphogenesis. We observed that nascent disks are invariably continuous with the ciliary plasma membrane, although, owing to partial enclosure, they can appear to be internal in 2D profiles. Tomographic analyses of the basal-most region of the outer segment show changes in shape of the ciliary plasma membrane indicating an invagination, which is likely a first step in disk formation. The invagination flattens to create the proximal surface of an evaginating lamella, as well as membrane protrusions that extend between adjacent lamellae, thereby initiating a disk rim. Immediately distal to this initiation site, lamellae of increasing diameter are evident, indicating growth outward from the cilium. In agreement with a previous model, our data indicate that mature disks are formed once lamellae reach full diameter, and the growth of a rim encloses the space between adjacent surfaces of two lamellae. This study provides 3D data of nascent and mature rod photoreceptor disk membranes at unprecedented z-axis depth and resolution, and provides a basis for addressing fundamental questions, ranging from protein sorting in the photoreceptor cilium to photoreceptor electrophysiology.

Smoothened-antagonists reverse homogentisic acid-induced alterations of Hedgehog signaling and primary cilium length in alkaptonuria.

PubMed

Gambassi, Silvia; Geminiani, Michela; Thorpe, Stephen D; Bernardini, Giulia; Millucci, Lia; Braconi, Daniela; Orlandini, Maurizio; Thompson, Clare L; Petricci, Elena; Manetti, Fabrizio; Taddei, Maurizio; Knight, Martin M; Santucci, Annalisa

2017-11-01

Alkaptonuria (AKU) is an ultra-rare genetic disease, in which the accumulation of a toxic metabolite, homogentisic acid (HGA) leads to the systemic development of ochronotic aggregates. These aggregates cause severe complications mainly at the level of joints with extensive degradation of the articular cartilage. Primary cilia have been demonstrated to play an essential role in development and the maintenance of articular cartilage homeostasis, through their involvement in mechanosignaling and Hedgehog signaling pathways. Hedgehog signaling has been demonstrated to be activated in osteoarthritis (OA) and to drive cartilage degeneration in vivo. The numerous similarities between OA and AKU suggest that primary cilia Hedgehog signaling may also be altered in AKU. Thus, we characterized an AKU cellular model in which healthy chondrocytes were treated with HGA (66 µM) to replicate AKU cartilage pathology. We investigated the degree of activation of the Hedgehog signaling pathway and how treatment with inhibitors of the receptor Smoothened (Smo) influenced Hedgehog activation and primary cilia structure. The results obtained in this work provide a further step in the comprehension of the pathophysiological features of AKU, suggesting a potential therapeutic approach to modulate AKU cartilage degradation processes through manipulation of the Hedgehog pathway. © 2016 Wiley Periodicals, Inc.

Primary cilia maintain corneal epithelial homeostasis by regulation of the Notch signaling pathway

PubMed Central

Grisanti, Laura; Revenkova, Ekaterina; Gordon, Ronald E.

2016-01-01

Primary cilia have been linked to signaling pathways involved in cell proliferation, cell motility and cell polarity. Defects in ciliary function result in developmental abnormalities and multiple ciliopathies. Patients affected by severe ciliopathies, such as Meckel syndrome, present several ocular surface disease conditions of unclear pathogenesis. Here, we show that primary cilia are predominantly present on basal cells of the mouse corneal epithelium (CE) throughout development and in the adult. Conditional ablation of cilia in the CE leads to an increase in proliferation and vertical migration of basal corneal epithelial cells (CECs). A consequent increase in cell density of suprabasal layers results in a thicker than normal CE. Surprisingly, in cilia-deficient CE, cilia-mediated signaling pathways, including Hh and Wnt pathways, were not affected but the intensity of Notch signaling was severely diminished. Although Notch1 and Notch2 receptors were expressed normally, nuclear Notch1 intracellular domain (N1ICD) expression was severely reduced. Postnatal development analysis revealed that in cilia-deficient CECs downregulation of the Notch pathway precedes cell proliferation defects. Thus, we have uncovered a function of the primary cilium in maintaining homeostasis of the CE by balancing proliferation and vertical migration of basal CECs through modulation of Notch signaling. PMID:27122169

Polycystin-1 Cleavage and the Regulation of Transcriptional Pathways

PubMed Central

Merrick, David; Bertuccio, Claudia A.; Chapin, Hannah C.; Lal, Mark; Chauvet, Veronique; Caplan, Michael J.

2013-01-01

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic cause of end stage renal disease, affecting ~1 in 1,000 people. The disease is characterized by the development of numerous large fluid filled renal cysts over the course of decades. These cysts compress the surrounding renal parenchyma and impair its function. Mutations in two genes are responsible for ADPKD. The protein products of both of these genes, polycystin-1 and polycystin-2, localize to the primary cilium and participate in a wide variety of signaling pathways. Polycystin-1 undergoes several proteolytic cleavages that produce fragments that manifest biological activities. Recent results suggest that the production of polycystin-1 cleavage fragments is necessary and sufficient to account for at least some, although certainly not all, of the physiological functions of the parent protein. PMID:23824180

Regulation of Hedgehog Signalling Inside and Outside the Cell

PubMed Central

Ramsbottom, Simon A.; Pownall, Mary E.

2016-01-01

The hedgehog (Hh) signalling pathway is conserved throughout metazoans and plays an important regulatory role in both embryonic development and adult homeostasis. Many levels of regulation exist that control the release, reception, and interpretation of the hedgehog signal. The fatty nature of the Shh ligand means that it tends to associate tightly with the cell membrane, and yet it is known to act as a morphogen that diffuses to elicit pattern formation. Heparan sulfate proteoglycans (HSPGs) play a major role in the regulation of Hh distribution outside the cell. Inside the cell, the primary cilium provides an important hub for processing the Hh signal in vertebrates. This review will summarise the current understanding of how the Hh pathway is regulated from ligand production, release, and diffusion, through to signal reception and intracellular transduction. PMID:27547735

Novel Insights into the Development and Function of Cilia Using the Advantages of the Paramecium Cell and Its Many Cilia

PubMed Central

Yano, Junji; Valentine, Megan S.; Van Houten, Judith L.

2015-01-01

Paramecium species, especially P. tetraurelia and caudatum, are model organisms for modern research into the form and function of cilia. In this review, we focus on the ciliary ion channels and other transmembrane proteins that control the beat frequency and wave form of the cilium by controlling the signaling within the cilium. We put these discussions in the context of the advantages that Paramecium brings to the understanding of ciliary motility: mutants for genetic dissections of swimming behavior, electrophysiology, structural analysis, abundant cilia for biochemistry and modern proteomics, genomics and molecular biology. We review the connection between behavior and physiology, which allows the cells to broadcast the function of their ciliary channels in real time. We build a case for the important insights and advantages that this model organism continues to bring to the study of cilia. PMID:26230712

High-speed broadband elastic actuator in water using induced-charge electro-osmosis with a skew structure.

PubMed

Sugioka, Hideyuki; Nakano, Naoki

2018-01-01

An artificial cilium using ac electro-osmosis (ACEO) is attractive because of its large potentiality for innovative microfluidic applications. However, the ACEO cilium has not been probed experimentally and has a shortcoming that the working frequency range is very narrow. Thus, we here propose an ACEO elastic actuator having a skew structure that broadens a working frequency range and experimentally demonstrate that the elastic actuator in water can be driven with a high-speed (∼10 Hz) and a wide frequency range (∼0.1 to ∼10 kHz). Moreover, we propose a simple self-consistent model that explains the broadband characteristic due to the skew structure with other characteristics. By comparing the theoretical results with the experimental results, we find that they agree fairly well. We believe that our ACEO elastic actuator will play an important role in microfluidics in the future.

High-speed broadband elastic actuator in water using induced-charge electro-osmosis with a skew structure

NASA Astrophysics Data System (ADS)

Sugioka, Hideyuki; Nakano, Naoki

2018-01-01

An artificial cilium using ac electro-osmosis (ACEO) is attractive because of its large potentiality for innovative microfluidic applications. However, the ACEO cilium has not been probed experimentally and has a shortcoming that the working frequency range is very narrow. Thus, we here propose an ACEO elastic actuator having a skew structure that broadens a working frequency range and experimentally demonstrate that the elastic actuator in water can be driven with a high-speed (˜10 Hz) and a wide frequency range (˜0.1 to ˜10 kHz). Moreover, we propose a simple self-consistent model that explains the broadband characteristic due to the skew structure with other characteristics. By comparing the theoretical results with the experimental results, we find that they agree fairly well. We believe that our ACEO elastic actuator will play an important role in microfluidics in the future.

Fabrication and Manipulation of Ciliary Microrobots with Non-reciprocal Magnetic Actuation

PubMed Central

Kim, Sangwon; Lee, Seungmin; Lee, Jeonghun; Nelson, Bradley J.; Zhang, Li; Choi, Hongsoo

2016-01-01

Magnetically actuated ciliary microrobots were designed, fabricated, and manipulated to mimic cilia-based microorganisms such as paramecia. Full three-dimensional (3D) microrobot structures were fabricated using 3D laser lithography to form a polymer base structure. A nickel/titanium bilayer was sputtered onto the cilia part of the microrobot to ensure magnetic actuation and biocompatibility. The microrobots were manipulated by an electromagnetic coil system, which generated a stepping magnetic field to actuate the cilia with non-reciprocal motion. The cilia beating motion produced a net propulsive force, resulting in movement of the microrobot. The magnetic forces on individual cilia were calculated with various input parameters including magnetic field strength, cilium length, applied field angle, actual cilium angle, etc., and the translational velocity was measured experimentally. The position and orientation of the ciliary microrobots were precisely controlled, and targeted particle transportation was demonstrated experimentally. PMID:27470077

Novel Insights into the Development and Function of Cilia Using the Advantages of the Paramecium Cell and Its Many Cilia.

PubMed

Yano, Junji; Valentine, Megan S; Van Houten, Judith L

2015-07-29

Paramecium species, especially P. tetraurelia and caudatum, are model organisms for modern research into the form and function of cilia. In this review, we focus on the ciliary ion channels and other transmembrane proteins that control the beat frequency and wave form of the cilium by controlling the signaling within the cilium. We put these discussions in the context of the advantages that Paramecium brings to the understanding of ciliary motility: mutants for genetic dissections of swimming behavior, electrophysiology, structural analysis, abundant cilia for biochemistry and modern proteomics, genomics and molecular biology. We review the connection between behavior and physiology, which allows the cells to broadcast the function of their ciliary channels in real time. We build a case for the important insights and advantages that this model organism continues to bring to the study of cilia.

Bistable synchronization modes in hydrodynamically coupled micro-rotors

NASA Astrophysics Data System (ADS)

Guo, Hanliang; Kanale, Anup; Fuerthauer, Sebastian; Kanso, Eva

2017-11-01

Cilia often beat in synchrony, and they may transition between different synchronization modes in the same cell type. For example, cilia in the mammalian brain ventricles are reported to periodically change their collective beat orientation, providing a cilia-based switch for redirecting the transport of cerebrospinal fluid. Experimental and theoretical evidences suggest that phase coordinations can be achieved solely via hydrodynamical interactions. However, the exact mechanisms responsible for transitioning between various synchronization modes remain illusive. Here, we use a theoretical model where each cilium is represented by a bead moving along a closed trajectory close to a no-slip surface. We investigate the emergent synchronization modes and their stability for various cilia-inspired force profiles. We observe distinct stable synchronization modes between two rotors, including a bistable regime where both in-phase and anti-phase synchronizations are stable. We then extend this analysis to an array of rotors where we demonstrate the dynamical formations of metachronal waves. These findings may help us to understand the origin of synchrony in biological and bio-inspired systems, and the mechanisms underlying transitions between different synchronization modes.

Microtubules Enable the Planar Cell Polarity of Airway Cilia

PubMed Central

Vladar, Eszter K.; Bayly, Roy D.; Sangoram, Ashvin; Scott, Matthew P.; Axelrod, Jeffrey D.

2012-01-01

Summary Background Airway cilia must be physically oriented along the longitudinal tissue axis for concerted, directional motility that is essential for proper mucociliary clearance. Results We show that Planar Cell Polarity (PCP) signaling specifies directionality and orients respiratory cilia. Within all airway epithelial cells a conserved set of PCP proteins shows interdependent, asymmetric junctional localization; non-autonomous signaling coordinates polarization between cells; and a polarized microtubule (MT) network is likely required for asymmetric PCP protein localization. We find that basal bodies dock after polarity of PCP proteins is established, are polarized nearly simultaneously, and refinement of basal body/cilium orientation continues during airway epithelial development. Unique to mature multiciliated cells, we identify PCP-regulated, planar polarized MTs that originate from basal bodies and interact, via their plus ends, with membrane domains associated with the PCP proteins Frizzled and Dishevelled. Disruption of MTs leads to misoriented cilia. Conclusions A conserved PCP pathway orients airway cilia by communicating polarity information from asymmetric membrane domains at the apical junctions, through MTs, to orient the MT and actin based network of ciliary basal bodies below the apical surface. PMID:23122850

The Oak Ridge Polycystic Kidney mouse: modeling ciliopathies of mice and men.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lehman, J M; Michaud III, Edward J; Schoeb, T

2008-08-01

The Oak Ridge Polycystic Kidney (ORPK) mouse was described nearly 14 years ago as a model for human recessive polycystic kidney disease. The ORPK mouse arose through integration of a transgene into an intron of the Ift88 gene resulting in a hypomorphic allele (Ift88Tg737Rpw). The Ift88Tg737Rpw mutation impairs intraflagellar transport (IFT), a process required for assembly of motile and immotile cilia. Historically, the primary immotile cilium was thought to have minimal importance for human health; however, a rapidly expanding number of human disorders have now been attributed to ciliary defects. Importantly, many of these phenotypes are present and can bemore » analyzed using the ORPK mouse. In this review, we highlight the research conducted using the OPRK mouse and the phenotypes shared with human cilia disorders. Furthermore, we describe an additional follicular dysplasia phenotype in the ORPK mouse, which alongside the ectodermal dysplasias seen in human Ellis-van Creveld and Sensenbrenner's syndromes, suggests an unappreciated role for primary cilia in the skin and hair follicle.« less

Silibinin negatively contributes to primary cilia length via autophagy regulated by histone deacetylase 6 in confluent mouse embryo fibroblast 3T3-L1 cells.

PubMed

Xu, Qian; Liu, Wei; Liu, Xiaoling; Liu, Weiwei; Wang, Hongju; Yao, Guodong; Zang, Linghe; Hayashi, Toshihiko; Tashiro, Shin-Ichi; Onodera, Satoshi; Ikejima, Takashi

2016-09-01

Primary cilium is a cellular antenna, signalling as a sensory organelle. Numerous pathological manifestation is associated with change of its length. Although the interaction between autophagy and primary cilia has been suggested, the role of autophagy in primary cilia length is largely unknown. In this study the primary cilia were immunostained and observed by using confocal fluorescence microscopy, and we found that silibinin, a natural flavonoid, shortened the length of primary cilia, meanwhile it also induced autophagy in 3T3-L1 cells. This study was designed to investigate the significance of silibinin-induced autophagy in primary ciliary structure in confluent mouse embryo fibroblast 3T3-L1 cells. Either blocking the autophagic flux with pre-treatment with the autophagy inhibitor, 3-methyladenine (3-MA), or transfection of siRNA targeting LC3 inhibited the reduction of cilia length caused by silibinin exposure. Autophagy induced by silibinin decreased expressions of the cilia-associated proteins, such as IFT88, KIF3a and Ac-tubulin, while 3-MA restored it, indicating that autophagy induced by silibinin led to a reduction of primary cilia length. Histone deacetylase 6 (HDAC6), which was suggested as a mediator of autophagy, was up-regulated by silibinin in a time-dependent manner. In addition, 3T3-L1 cells treated with siRNA against HDAC6 had a reduced autophagic level and were protected from silibinin-induced cilia shortening. Taken together, we conclude that the HDAC6-mediated autophagy negatively regulates primary cilia length during silibinin treatment and has the potential to serve as a therapeutic target for primary cilia-associated ciliopathies. These findings thus provide new information about the potential link between autophagy and primary cilia.

Regulation of centriolar satellite integrity and its physiology.

PubMed

Hori, Akiko; Toda, Takashi

2017-01-01

Centriolar satellites comprise cytoplasmic granules that are located around the centrosome. Their molecular identification was first reported more than a quarter of a century ago. These particles are not static in the cell but instead constantly move around the centrosome. Over the last decade, significant advances in their molecular compositions and biological functions have been achieved due to comprehensive proteomics and genomics, super-resolution microscopy analyses and elegant genetic manipulations. Centriolar satellites play pivotal roles in centrosome assembly and primary cilium formation through the delivery of centriolar/centrosomal components from the cytoplasm to the centrosome. Their importance is further underscored by the fact that mutations in genes encoding satellite components and regulators lead to various human disorders such as ciliopathies. Moreover, the most recent findings highlight dynamic structural remodelling in response to internal and external cues and unexpected positive feedback control that is exerted from the centrosome for centriolar satellite integrity.

Primary cilia in gastric Gastrointestinal Stromal Tumours (GISTs): an ultrastructural study

PubMed Central

Castiella, Tomás; Muñoz, Guillermo; Luesma, María José; Santander, Sonia; Soriano, Mario; Junquera, Concepción

2013-01-01

Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal (non-epithelial) neoplasms of the human gastrointestinal (GI) tract. They are thought to derive from interstitial cells of Cajal (ICCs) or an ICC progenitor based on immunophenotypical and ultrastructural similarities. Because ICCs show primary cilium, our hypothesis is based on the possibility that some of these neoplastic cells could also present it. To determine this, an exhaustive ultrastructural study has been developed on four gastric GISTs. Previous studies had demonstrated considerable variability in tumour cells with two dominating phenotypes, spindly and epithelioid. In addition to these two types, we have found another cell type reminiscent of adult ICCs with a voluminous nucleus surrounded by narrow perinuclear cytoplasm with long slender cytoplasmic processes. We have also noted the presence of small undifferentiated cells. In this study, we report for the first time the presence of primary cilia (PCs) in spindle and epithelioid tumour cells, an ultrastructural feature we consider of special interest that has hitherto been ignored in the literature dealing with the ultrastructure of GISTs. We also point out the frequent occurrence of multivesicular bodies (MVBs). The ultrastructural findings described in gastric GISTs in this study appear to be relevant considering the critical roles played by PCs and MVBs recently demonstrated in tumourigenic processes. PMID:23672577

Minding the Gap: Factors Associated With Primary Care Coordination of Adults in 11 Countries.

PubMed

Penm, Jonathan; MacKinnon, Neil J; Strakowski, Stephen M; Ying, Jun; Doty, Michelle M

2017-03-01

Care coordination has been identified as a key strategy in improving the effectiveness, safety, and efficiency of the US health care system. Our objective was to determine whether population or health care system issues are associated with primary care coordination gaps in the United States and other high-income countries. We analyzed data from the 2013 Commonwealth Fund International Health Policy (IHP) survey with multivariate logistic regression analysis. Respondents were adult primary care patients from 11 countries: Australia, Canada, France, Germany, the Netherlands, New Zealand, Norway, Sweden, Switzerland, United Kingdom, and the United States. Poor primary care coordination was defined as participants reporting at least 3 gaps in the coordination of care out of a maximum of 5. Analyses were based on 13,958 respondents. The rate of poor primary care coordination was 5.2% (724/13,958 respondents) overall and highest in the United States, at 9.8% (137/1,395 respondents). Multivariate regression analysis among all respondents found that they were less likely to experience poor primary care coordination if their primary care physician often or always knew their medical history, spent sufficient time, involved them, and explained things well (odds ratio = 0.6 for each). Poor primary care coordination was more likely to occur among patients with chronic conditions (odds ratios = 1.4-2.1 depending on number) and patients younger than 65 years (odds ratios = 1.6-2.3 depending on age-group). Among US respondents, insurance status, health status, household income, and sex were not associated with poor primary care coordination. The United States had the highest rate of poor primary care coordination among the 11 high-income countries evaluated. An established relationship with a primary care physician was significantly associated with better care coordination, whereas being chronically ill or younger was associated with poorer care coordination. © 2017 Annals of Family Medicine, Inc.

Minding the Gap: Factors Associated With Primary Care Coordination of Adults in 11 Countries

PubMed Central

Penm, Jonathan; MacKinnon, Neil J.; Strakowski, Stephen M.; Ying, Jun; Doty, Michelle M.

2017-01-01

PURPOSE Care coordination has been identified as a key strategy in improving the effectiveness, safety, and efficiency of the US health care system. Our objective was to determine whether population or health care system issues are associated with primary care coordination gaps in the United States and other high-income countries. METHODS We analyzed data from the 2013 Commonwealth Fund International Health Policy (IHP) survey with multivariate logistic regression analysis. Respondents were adult primary care patients from 11 countries: Australia, Canada, France, Germany, the Netherlands, New Zealand, Norway, Sweden, Switzerland, United Kingdom, and the United States. Poor primary care coordination was defined as participants reporting at least 3 gaps in the coordination of care out of a maximum of 5. RESULTS Analyses were based on 13,958 respondents. The rate of poor primary care coordination was 5.2% (724/13,958 respondents) overall and highest in the United States, at 9.8% (137/1,395 respondents). Multivariate regression analysis among all respondents found that they were less likely to experience poor primary care coordination if their primary care physician often or always knew their medical history, spent sufficient time, involved them, and explained things well (odds ratio = 0.6 for each). Poor primary care coordination was more likely to occur among patients with chronic conditions (odds ratios = 1.4–2.1 depending on number) and patients younger than 65 years (odds ratios = 1.6–2.3 depending on age-group). Among US respondents, insurance status, health status, household income, and sex were not associated with poor primary care coordination. CONCLUSIONS The United States had the highest rate of poor primary care coordination among the 11 high-income countries evaluated. An established relationship with a primary care physician was significantly associated with better care coordination, whereas being chronically ill or younger was associated with poorer care coordination. PMID:28289109

Fabrication and characterization of a magnetic micro-actuator based on deformable Fe-doped PDMS artificial cilium using 3D printing

NASA Astrophysics Data System (ADS)

Liu, Fengli; Alici, Gursel; Zhang, Binbin; Beirne, Stephen; Li, Weihua

2015-03-01

This paper proposes the use of a 3D extrusion printer to fabricate artificial magnetic cilium. The cilia are fabricated using polydimethylsiloxane (PDMS) doped with iron particles so that they remain slender and flexible. They can be driven by a magnetic field to closely mimic the behaviour of biological cilia. Doping iron particles to the polymers has already been done; however, to the best of our knowledge, printing such active and soft magnetic structures has not. The existing methods for manufacturing magnetic polymeric structures are complex and difficult to use for the fabrication of micro-sized high-aspect-ratio cilia. The 3D printing technique we propose here is simple and inexpensive compared to previously suggested fabrication methods. In this study, free-standing magnetic PDMS cilia were fabricated in different sizes up to 5 mm in length and 1 mm in width. The stress-strain curves of the PDMS cilia were experimentally obtained to quantify the effect of the concentration of the iron particles on the modulus of elasticity of the cilia. The higher the iron concentration, the higher the modulus of elasticity. We have quantified the characteristics of the cilia made of 40% w/w iron particles in PDMS. A single cilium (5 × 1 × 0.0035 mm) can output up to 27 μN blocking force under a magnetic field of 160 mT. These cilia can be used as a mixer in lap-on-chip applications and as the anchoring and propulsion legs of endoscopic capsule robots operating within the gastrointestinal tract of humans. Analytical expressions estimating the blocking force are established and compared with the experimental results.

MKS1 regulates ciliary INPP5E levels in Joubert syndrome

PubMed Central

Slaats, Gisela G.; Isabella, Christine R.; Kroes, Hester Y.; Dempsey, Jennifer C.; Gremmels, Hendrik; Monroe, Glen R.; Phelps, Ian G.; Duran, Karen J.; Adkins, Jonathan; Kumar, Sairam A.; Knutzen, Dana M.; Knoers, Nine V.; Mendelsohn, Nancy J.; Neubauer, David; Mastroyianni, Sotiria D.; Vogt, Julie; Worgan, Lisa; Karp, Natalya; Bowdin, Sarah; Glass, Ian A.; Parisi, Melissa A.; Otto, Edgar A.; Johnson, Colin A.; Hildebrandt, Friedhelm; van Haaften, Gijs; Giles, Rachel H.; Doherty, Dan

2016-01-01

Background Joubert syndrome (JS) is a recessive ciliopathy characterized by a distinctive brain malformation “the molar tooth sign”. Mutations in >27 genes cause JS, and mutations in 12 of these genes also cause Meckel syndrome (MKS). The goals of this work are to describe the clinical features of MKS1-related JS and determine whether disease causing MKS1 mutations affect cellular phenotypes such as cilium number, length and protein content as potential mechanisms underlying JS. Methods We measured cilium number, length and protein content (ARL13B and INPP5E) by immunofluorescence in fibroblasts from individuals with MKS1-related JS and in a 3D spheroid rescue assay to test the effects of disease-related MKS1 mutations. Results We report MKS1 mutations (eight of them previously unreported) in nine individuals with JS. A minority of the individuals with MKS1-related JS have MKS features. In contrast to the truncating mutations associated with MKS, all of the individuals with MKS1-related JS carry ≥1 non-truncating mutation. Fibroblasts from individuals with MKS1-related JS make normal or fewer cilia than control fibroblasts, their cilia are more variable in length than controls, and show decreased ciliary ARL13B and INPP5E. Additionally, MKS1 mutant alleles have similar effects in 3D spheroids. Conclusions MKS1 functions in the transition zone at the base of the cilium to regulate ciliary INPP5E content, through an ARL13B-dependent mechanism. Mutations in INPP5E also cause JS, so our findings in patient fibroblasts support the notion that loss of INPP5E function, due to either mutation or mislocalization, is a key mechanism underlying JS, downstream of MKS1 and ARL13B. PMID:26490104

Untangling ciliary access and enrichment of two rhodopsin-like receptors using quantitative fluorescence microscopy reveals cell-specific sorting pathways

PubMed Central

Geneva, Ivayla I.; Tan, Han Yen; Calvert, Peter D.

2017-01-01

Resolution limitations of optical systems are major obstacles for determining whether proteins are enriched within cell compartments. Here we use an approach to determine the degree of membrane protein ciliary enrichment that quantitatively accounts for the differences in sampling of the ciliary and apical membranes inherent to confocal microscopes. Theory shows that cilia will appear more than threefold brighter than the surrounding apical membrane when the densities of fluorescently labeled proteins are the same, thus providing a benchmark for ciliary enrichment. Using this benchmark, we examined the ciliary enrichment signals of two G protein–coupled receptors (GPCRs)—the somatostatin receptor 3 and rhodopsin. Remarkably, we found that the C-terminal VxPx motif, required for efficient enrichment of rhodopsin within rod photoreceptor sensory cilia, inhibited enrichment of the somatostatin receptor in primary cilia. Similarly, VxPx inhibited primary cilium enrichment of a chimera of rhodopsin and somatostatin receptor 3, where the dual Ax(S/A)xQ ciliary targeting motifs within the third intracellular loop of the somatostatin receptor replaced the third intracellular loop of rhodopsin. Rhodopsin was depleted from primary cilia but gained access, without being enriched, with the dual Ax(S/A)xQ motifs. Ciliary enrichment of these GPCRs thus operates via distinct mechanisms in different cells. PMID:27974638

Optimal ciliary beating patterns

NASA Astrophysics Data System (ADS)

Vilfan, Andrej; Osterman, Natan

2011-11-01

We introduce a measure for energetic efficiency of single or collective biological cilia. We define the efficiency of a single cilium as Q2 / P , where Q is the volume flow rate of the pumped fluid and P is the dissipated power. For ciliary arrays, we define it as (ρQ) 2 / (ρP) , with ρ denoting the surface density of cilia. We then numerically determine the optimal beating patterns according to this criterion. For a single cilium optimization leads to curly, somewhat counterintuitive patterns. But when looking at a densely ciliated surface, the optimal patterns become remarkably similar to what is observed in microorganisms like Paramecium. The optimal beating pattern then consists of a fast effective stroke and a slow sweeping recovery stroke. Metachronal waves lead to a significantly higher efficiency than synchronous beating. Efficiency also increases with an increasing density of cilia up to the point where crowding becomes a problem. We finally relate the pumping efficiency of cilia to the swimming efficiency of a spherical microorganism and show that the experimentally estimated efficiency of Paramecium is surprisingly close to the theoretically possible optimum.

Measuring primary care organizational capacity for diabetes care coordination: the Diabetes Care Coordination Readiness Assessment.

PubMed

Weeks, Douglas L; Polello, Jennifer M; Hansen, Daniel T; Keeney, Benjamin J; Conrad, Douglas A

2014-01-01

Not all primary care clinics are prepared to implement care coordination services for chronic conditions, such as diabetes. Understanding true capacity to coordinate care is an important first-step toward establishing effective and efficient care coordination. Yet, we could identify no diabetes-specific instruments to systematically assess readiness and/or status of primary care clinics to engage in diabetes care coordination. This report describes the development and initial validation of the Diabetes Care Coordination Readiness Assessment (DCCRA), which is intended to measure primary care clinic readiness to coordinate care for adult patients with diabetes. The instrument was developed through iterative item generation within a framework of five domains of care coordination: Organizational Capacity, Care Coordination, Clinical Management, Quality Improvement, and Technical Infrastructure. Validation data was collected on 39 primary care clinics. Content validity, inter-rater reliability, internal consistency, and construct validity of the 49-item instrument were assessed. Inter-rater agreement indices per item ranged from 0.50 to 1.0. Cronbach's alpha of the entire instrument was 0.964, and for the five domain scales ranged from 0.688 to 0.961. Clinics with existing care coordinators were rated as more ready to support care coordination than clinics without care coordinators for the entire DCCRA and for each domain, supporting construct validity. As providers increasingly attempt to adopt patient-centered approaches, introduction of the DCCRA is timely and appropriate for assisting clinics with identifying gaps in provision of care coordination services. The DCCRA's strengths include promising psychometric properties. A valid measure of diabetes care coordination readiness should be useful in diabetes program evaluation, assistance with quality improvement initiatives, and measurement of patient-centered care in research.

Chemical and Biological Studies of Nakiterpiosin and Nakiterpiosinone

PubMed Central

Gao, Shuanhu; Wang, Qiaoling; Huang, Lily Jun-Shen; Lum, Lawrence; Chen, Chuo

2009-01-01

Nakiterpiosin and nakiterpiosinone are two related C-nor-D-homosteroids isolated from the sponge Terpios hoshinota that show promise as anti-cancer agents. We have previously described the asymmetric synthesis and the revision of the relative configuration of nakiterpiosin. We now provide detailed information on the stereochemical analysis that supports our structure revision and the synthesis of the originally proposed and revised nakiterpiosin. In addition, we herein describe a refined approach for the synthesis of nakiterpiosin, the first synthesis of nakiterpiosinone, and preliminary mechanistic studies of nakiterpiosin's action in mammalian cells. Cells treated with nakiterpiosin exhibit compromised formation of the primary cilium, an organelle that functions as an assembly point for components of the Hedgehog signal transduction pathway. We provide evidence that the biological effects exhibited by nakiterpiosin are mechanistically distinct from those of well-established anti-mitotic agents such as taxol. Nakiterpiosin may be useful as an anti-cancer agent in those tumors resistant to existing anti-mitotic agents and those dependent on Hedgehog pathway responses for growth. PMID:20000429

Asymmetric segregation of the double-stranded RNA binding protein Staufen2 during mammalian neural stem cell divisions promotes lineage progression.

PubMed

Kusek, Gretchen; Campbell, Melissa; Doyle, Frank; Tenenbaum, Scott A; Kiebler, Michael; Temple, Sally

2012-10-05

Asymmetric cell divisions are a fundamental feature of neural development, and misregulation can lead to brain abnormalities or tumor formation. During an asymmetric cell division, molecular determinants are segregated preferentially into one daughter cell to specify its fate. An important goal is to identify the asymmetric determinants in neural progenitor cells, which could be tumor suppressors or inducers of specific neural fates. Here, we show that the double-stranded RNA-binding protein Stau2 is distributed asymmetrically during progenitor divisions in the developing mouse cortex, preferentially segregating into the Tbr2(+) neuroblast daughter, taking with it a subset of RNAs. Knockdown of Stau2 stimulates differentiation and overexpression produces periventricular neuronal masses, demonstrating its functional importance for normal cortical development. We immunoprecipitated Stau2 to examine its cargo mRNAs, and found enrichment for known asymmetric and basal cell determinants, such as Trim32, and identified candidates, including a subset involved in primary cilium function. Copyright © 2012 Elsevier Inc. All rights reserved.

Asymmetric Segregation of the Double-Stranded RNA Binding Protein Staufen2 during Mammalian Neural Stem Cell Divisions Promotes Lineage Progression

PubMed Central

Kusek, Gretchen; Campbell, Melissa; Doyle, Frank; Tenenbaum, Scott A.; Kiebler, Michael; Temple, Sally

2012-01-01

Summary Asymmetric cell divisions are a fundamental feature of neural development, and misregulation can lead to brain abnormalities or tumor formation. During an asymmetric cell division, molecular determinants are segregated preferentially into one daughter cell to specify its fate. An important goal is to identify the asymmetric determinants in neural progenitor cells, which could be tumor suppressors or inducers of specific neural fates. Here we show that the double-stranded RNA-binding protein Stau2 is distributed asymmetrically during progenitor divisions in the developing mouse cortex, preferentially segregating into the Tbr2+ neuroblast daughter, taking with it a sub-set of RNAs. Knockdown of Stau2 stimulates differentiation and over-expression produces periventricular neuronal masses, demonstrating its functional importance for normal cortical development. We immunoprecipitated Stau2 to examine its cargo mRNAs, and found enrichment for known asymmetric and basal cell determinants, such as Trim32, and identified novel candidates, including a subset involved in primary cilium function. PMID:22902295

Joubert syndrome: congenital cerebellar ataxia with the “molar tooth”

PubMed Central

Romani, Marta; Micalizzi, Alessia; Valente, Enza Maria

2013-01-01

Joubert syndrome (JS) is a congenital cerebellar ataxia with autosomal recessive or X-linked inheritance, which diagnostic hallmark is a unique cerebellar and brainstem malformation recognizable on brain imaging, the “molar tooth sign”. Neurological signs are present from neonatal age and include hypotonia evolving into ataxia, global developmental delay, ocular motor apraxia and breathing dysregulation. These are variably associated with multiorgan involvement, mainly of the retina, kidneys, skeleton and liver. To date, 21 causative genes have been identified, all encoding for proteins of the primary cilium or its apparatus. This is a subcellular organelle that plays key roles in development and in many cellular functions, making JS part of the expanding family of ciliopathies. There is marked clinical and genetic overlap among distinct ciliopathies, which may co-occur even within families. Such variability is likely explained by an oligogenic model of inheritance, in which mutations, rare variants and polymorphisms at distinct loci interplay to modulate the expressivity of the ciliary phenotype. PMID:23870701

Inversin, the gene product mutated in nephronophthisis type II, functions as a molecular switch between Wnt signaling pathways

PubMed Central

Simons, Matias; Gloy, Joachim; Ganner, Athina; Bullerkotte, Axel; Bashkurov, Mikhail; Krönig, Corinna; Schermer, Bernhard; Benzing, Thomas; Cabello, Olga A; Jenny, Andreas; Mlodzik, Marek; Polok, Bozena; Driever, Wolfgang; Obara, Tomoko; Walz, Gerd

2013-01-01

Cystic renal diseases are caused by mutations of proteins that share a unique subcellular localization: the primary cilium of tubular epithelial cells1. Mutations of the ciliary protein inversin cause nephronophthisis type II, an autosomal recessive cystic kidney disease characterized by extensive renal cysts, situs inversus and renal failure2. Here we report that inversin acts as a molecular switch between different Wnt signaling cascades. Inversin inhibits the canonical Wnt pathway by targeting cytoplasmic dishevelled (Dsh or Dvl1) for degradation; concomitantly, it is required for convergent extension movements in gastrulating Xenopus laevis embryos and elongation of animal cap explants, both regulated by noncanonical Wnt signaling. In zebrafish, the structurally related switch molecule diversin ameliorates renal cysts caused by the depletion of inversin, implying that an inhibition of canonical Wnt signaling is required for normal renal development. Fluid flow increases inversin levels in ciliated tubular epithelial cells and seems to regulate this crucial switch between Wnt signaling pathways during renal development. PMID:15852005

A Conserved Role for Girdin in Basal Body Positioning and Ciliogenesis.

PubMed

Nechipurenko, Inna V; Olivier-Mason, Anique; Kazatskaya, Anna; Kennedy, Julie; McLachlan, Ian G; Heiman, Maxwell G; Blacque, Oliver E; Sengupta, Piali

2016-09-12

Primary cilia are ubiquitous sensory organelles that mediate diverse signaling pathways. Cilia position on the cell surface is determined by the location of the basal body (BB) that templates the cilium. The mechanisms that regulate BB positioning in the context of ciliogenesis are largely unknown. Here we show that the conserved signaling and scaffolding protein Girdin localizes to the proximal regions of centrioles and regulates BB positioning and ciliogenesis in Caenorhabditis elegans sensory neurons and human RPE-1 cells. Girdin depletion alters localization of the intercentriolar linker and ciliary rootlet component rootletin, and rootletin knockdown in RPE-1 cells mimics Girdin-dependent phenotypes. C. elegans Girdin also regulates localization of the apical junction component AJM-1, suggesting that in nematodes Girdin may position BBs via rootletin- and AJM-1-dependent anchoring to the cytoskeleton and plasma membrane, respectively. Together, our results describe a conserved role for Girdin in BB positioning and ciliogenesis. Copyright © 2016 Elsevier Inc. All rights reserved.

Ciliary dyslexia candidate genes DYX1C1 and DCDC2 are regulated by Regulatory Factor X (RFX) transcription factors through X-box promoter motifs

PubMed Central

Tammimies, Kristiina; Bieder, Andrea; Lauter, Gilbert; Sugiaman-Trapman, Debora; Torchet, Rachel; Hokkanen, Marie-Estelle; Burghoorn, Jan; Castrén, Eero; Kere, Juha; Tapia-Páez, Isabel; Swoboda, Peter

2016-01-01

DYX1C1, DCDC2, and KIAA0319 are three of the most replicated dyslexia candidate genes (DCGs). Recently, these DCGs were implicated in functions at the cilium. Here, we investigate the regulation of these DCGs by Regulatory Factor X transcription factors (RFX TFs), a gene family known for transcriptionally regulating ciliary genes. We identify conserved X-box motifs in the promoter regions of DYX1C1, DCDC2, and KIAA0319 and demonstrate their functionality, as well as the ability to recruit RFX TFs using reporter gene and electrophoretic mobility shift assays. Furthermore, we uncover a complex regulation pattern between RFX1, RFX2, and RFX3 and their significant effect on modifying the endogenous expression of DYX1C1 and DCDC2 in a human retinal pigmented epithelial cell line immortalized with hTERT (hTERT-RPE1). In addition, induction of ciliogenesis increases the expression of RFX TFs and DCGs. At the protein level, we show that endogenous DYX1C1 localizes to the base of the cilium, whereas DCDC2 localizes along the entire axoneme of the cilium, thereby validating earlier localization studies using overexpression models. Our results corroborate the emerging role of DCGs in ciliary function and characterize functional noncoding elements, X-box promoter motifs, in DCG promoter regions, which thus can be targeted for mutation screening in dyslexia and ciliopathies associated with these genes.—Tammimies, K., Bieder, A., Lauter, G., Sugiaman-Trapman, D., Torchet, R., Hokkanen, M.-E., Burghoorn, J., Castrén, E., Kere, J., Tapia-Páez, I., Swoboda, P. Ciliary dyslexia candidate genes DYX1C1 and DCDC2 are regulated by Regulatory Factor (RF) X transcription factors through X-box promoter motifs. PMID:27451412

Ciliary dyslexia candidate genes DYX1C1 and DCDC2 are regulated by Regulatory Factor X (RFX) transcription factors through X-box promoter motifs.

PubMed

Tammimies, Kristiina; Bieder, Andrea; Lauter, Gilbert; Sugiaman-Trapman, Debora; Torchet, Rachel; Hokkanen, Marie-Estelle; Burghoorn, Jan; Castrén, Eero; Kere, Juha; Tapia-Páez, Isabel; Swoboda, Peter

2016-10-01

DYX1C1, DCDC2, and KIAA0319 are three of the most replicated dyslexia candidate genes (DCGs). Recently, these DCGs were implicated in functions at the cilium. Here, we investigate the regulation of these DCGs by Regulatory Factor X transcription factors (RFX TFs), a gene family known for transcriptionally regulating ciliary genes. We identify conserved X-box motifs in the promoter regions of DYX1C1, DCDC2, and KIAA0319 and demonstrate their functionality, as well as the ability to recruit RFX TFs using reporter gene and electrophoretic mobility shift assays. Furthermore, we uncover a complex regulation pattern between RFX1, RFX2, and RFX3 and their significant effect on modifying the endogenous expression of DYX1C1 and DCDC2 in a human retinal pigmented epithelial cell line immortalized with hTERT (hTERT-RPE1). In addition, induction of ciliogenesis increases the expression of RFX TFs and DCGs. At the protein level, we show that endogenous DYX1C1 localizes to the base of the cilium, whereas DCDC2 localizes along the entire axoneme of the cilium, thereby validating earlier localization studies using overexpression models. Our results corroborate the emerging role of DCGs in ciliary function and characterize functional noncoding elements, X-box promoter motifs, in DCG promoter regions, which thus can be targeted for mutation screening in dyslexia and ciliopathies associated with these genes.-Tammimies, K., Bieder, A., Lauter, G., Sugiaman-Trapman, D., Torchet, R., Hokkanen, M.-E., Burghoorn, J., Castrén, E., Kere, J., Tapia-Páez, I., Swoboda, P. Ciliary dyslexia candidate genes DYX1C1 and DCDC2 are regulated by Regulatory Factor (RF) X transcription factors through X-box promoter motifs. © The Author(s).

MKS1 regulates ciliary INPP5E levels in Joubert syndrome.

PubMed

Slaats, Gisela G; Isabella, Christine R; Kroes, Hester Y; Dempsey, Jennifer C; Gremmels, Hendrik; Monroe, Glen R; Phelps, Ian G; Duran, Karen J; Adkins, Jonathan; Kumar, Sairam A; Knutzen, Dana M; Knoers, Nine V; Mendelsohn, Nancy J; Neubauer, David; Mastroyianni, Sotiria D; Vogt, Julie; Worgan, Lisa; Karp, Natalya; Bowdin, Sarah; Glass, Ian A; Parisi, Melissa A; Otto, Edgar A; Johnson, Colin A; Hildebrandt, Friedhelm; van Haaften, Gijs; Giles, Rachel H; Doherty, Dan

2016-01-01

Joubert syndrome (JS) is a recessive ciliopathy characterised by a distinctive brain malformation 'the molar tooth sign'. Mutations in >27 genes cause JS, and mutations in 12 of these genes also cause Meckel-Gruber syndrome (MKS). The goals of this work are to describe the clinical features of MKS1-related JS and determine whether disease causing MKS1 mutations affect cellular phenotypes such as cilium number, length and protein content as potential mechanisms underlying JS. We measured cilium number, length and protein content (ARL13B and INPP5E) by immunofluorescence in fibroblasts from individuals with MKS1-related JS and in a three-dimensional (3D) spheroid rescue assay to test the effects of disease-related MKS1 mutations. We report MKS1 mutations (eight of them previously unreported) in nine individuals with JS. A minority of the individuals with MKS1-related JS have MKS features. In contrast to the truncating mutations associated with MKS, all of the individuals with MKS1-related JS carry ≥ 1 non-truncating mutation. Fibroblasts from individuals with MKS1-related JS make normal or fewer cilia than control fibroblasts, their cilia are more variable in length than controls, and show decreased ciliary ARL13B and INPP5E. Additionally, MKS1 mutant alleles have similar effects in 3D spheroids. MKS1 functions in the transition zone at the base of the cilium to regulate ciliary INPP5E content, through an ARL13B-dependent mechanism. Mutations in INPP5E also cause JS, so our findings in patient fibroblasts support the notion that loss of INPP5E function, due to either mutation or mislocalisation, is a key mechanism underlying JS, downstream of MKS1 and ARL13B. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

42 CFR 438.208 - Coordination and continuity of care.

Code of Federal Regulations, 2013 CFR

2013-10-01

... MCO must meet the primary care coordination, identification, assessment, and treatment planning... enrollees. (b) Primary care and coordination of health care services for all MCO, PIHP, and PAHP enrollees... 42 Public Health 4 2013-10-01 2013-10-01 false Coordination and continuity of care. 438.208...

Patient, Primary Care Provider, and Specialist Perspectives on Specialty Care Coordination in an Integrated Health Care System.

PubMed

Vimalananda, Varsha G; Dvorin, Kelly; Fincke, B Graeme; Tardiff, Nicole; Bokhour, Barbara G

Successful coordination of specialty care requires understanding the perspectives of patients, primary care providers, and specialists-that is, the specialty care "triad." This study used qualitative methods to compare these perspectives in an integrated health care system, using diabetes specialty care as an exemplar. Primary care providers and endocrinologists relied on interclinician relationships to coordinate care. Clinicians rarely included patients or other staff in their conceptualization of specialty care coordination. Patients often assumed responsibility for specialty care coordination but struggled to succeed. We identified several opportunities to improve coordination across the triad. In an integrated medical system, the shared organizational structure can facilitate these efforts.

Patient-reported care coordination: associations with primary care continuity and specialty care use.

PubMed

Liss, David T; Chubak, Jessica; Anderson, Melissa L; Saunders, Kathleen W; Tuzzio, Leah; Reid, Robert J

2011-01-01

Care coordination is increasingly recognized as a necessary element of high-quality, patient-centered care. This study investigated (1) the association between care coordination and continuity of primary care, and (2) differences in this association by level of specialty care use. We conducted a cross-sectional study of Medicare enrollees with select chronic conditions in an integrated health care delivery system in Washington State. We collected survey information on patient experiences and automated health care utilization data for 1 year preceding survey completion. Coordination was defined by the coordination measure from the short form of the Ambulatory Care Experiences Survey (ACES). Continuity was measured by primary care visit concentration. Patients who had 10 or more specialty care visits were classified as high users. Linear regression was used to estimate the association between coordination and continuity, controlling for potential confounders and clustering within clinicians. We used a continuity-by-specialty interaction term to determine whether the continuity-coordination association was modified by high specialty care use. Among low specialty care users, an increase of 1 standard deviation (SD) in continuity was associated with an increase of 2.71 in the ACES coordination scale (P <.001). In high specialty care users, we observed no association between continuity and reported coordination (P= .77). High use of specialty care may strain the ability of primary care clinicians to coordinate care effectively. Future studies should investigate care coordination interventions that allow for appropriate specialty care referrals without diminishing the ability of primary care physicians to manage overall patient care.

Improving care coordination in the specialty referral process between primary and specialty care.

PubMed

Lin, Caroline Y

2012-01-01

There is growing evidence of sub-optimal care coordination in the US. Care coordination includes the specialty referral process, which involves referral decision-making and information transfer between primary and specialty care. This article summarizes the evidence of sub-optimal care coordination in this process, as well as potential strategies to improve it.

Drosophila Ana1 is required for centrosome assembly and centriole elongation

PubMed Central

Saurya, Saroj; Roque, Hélio; Novak, Zsofia A.; Wainman, Alan; Aydogan, Mustafa G.; Volanakis, Adam; Sieber, Boris; Pinto, David Miguel Susano

2016-01-01

ABSTRACT Centrioles organise centrosomes and cilia, and these organelles have an important role in many cell processes. In flies, the centriole protein Ana1 is required for the assembly of functional centrosomes and cilia. It has recently been shown that Cep135 (also known as Bld10) initially recruits Ana1 to newly formed centrioles, and that Ana1 then recruits Asl (known as Cep152 in mammals) to promote the conversion of these centrioles into centrosomes. Here, we show that ana1 mutants lack detectable centrosomes in vivo, that Ana1 is irreversibly incorporated into centrioles during their assembly and appears to play a more important role in maintaining Asl at centrioles than in initially recruiting Asl to centrioles. Unexpectedly, we also find that Ana1 promotes centriole elongation in a dose-dependent manner: centrioles are shorter when Ana1 dosage is reduced and are longer when Ana1 is overexpressed. This latter function of Ana1 appears to be distinct from its role in centrosome and cilium function, as a GFP–Ana1 fusion lacking the N-terminal 639 amino acids of the protein can support centrosome assembly and cilium function but cannot promote centriole over-elongation when overexpressed. PMID:27206860

Hair sensor using a photoelectronic principle for sensing airflow and its direction

NASA Astrophysics Data System (ADS)

Huang, Kuang-Yuh; Huang, Chien-Tai

2011-01-01

Many organisms have diverse hair cells to instantaneously perceive the change of surroundings so that they can keep away from threats. These organs can precisely detect the tiny variations of airflow, water flow, sound, or pressure, and also resolve their affecting directions. Through this brilliant inspiration by the insects' cilia, we decided to design and develop a hair sensor for detecting two-dimensional airflow and pressure waves by using photoelectronic principles. The hair sensor inherently consists of an artificial cilium supported by an elastic membrane. A light-emitting diode and a quadrant photodiode are used as the photoelectronic sensor. The airflow or pressure wave directly stimulates the cilium to sway, and this motion contributes to let the projected light beam shift over the quadrant photodiode, whose four photodiodes produce then corresponding output signals. Because of dynamic and high-sensitive properties of the photoelectronic sensor, the hair sensor we developed possesses a high measurement resolution to be able to detect very tiny stimulation and its affecting direction. According to its multifaceted characteristics and simple structure, the hair sensor can be applied in numerous potential application fields, such as intrusion alarm system, noise detection system, as well as a tactile sensor.

Head sensory organs of Dactylopodola baltica (Macrodasyida, Gastrotricha): a combination of transmission electron microscopical and immunocytochemical techniques.

PubMed

Liesenjohann, Thilo; Neuhaus, Birger; Schmidt-Rhaesa, Andreas

2006-08-01

The anterior and posterior head sensory organs of Dactylopodola baltica (Macrodasyida, Gastrotricha) were investigated by transmission electron microscopy (TEM). In addition, whole individuals were labeled with phalloidin to mark F-actin and with anti-alpha-tubulin antibodies to mark microtubuli and studied with confocal laser scanning microscopy. Immunocytochemistry reveals that the large number of ciliary processes in the anterior head sensory organ contain F-actin; no signal could be detected for alpha-tubulin. Labeling with anti-alpha-tubulin antibodies revealed that the anterior and posterior head sensory organs are innervated by a common stem of nerves from the lateral nerve cords just anterior of the dorsal brain commissure. TEM studies showed that the anterior head sensory organ is composed of one sheath cell and one sensory cell with a single branching cilium that possesses a basal inflated part and regularly arranged ciliary processes. Each ciliary process contains one central microtubule. The posterior head sensory organ consists of at least one pigmented sheath cell and several probably monociliary sensory cells. Each cilium branches into irregularly arranged ciliary processes. These characters are assumed to belong to the ground pattern of the Gastrotricha. Copyright 2006 Wiley-Liss, Inc.

How personal and standardized coordination impact implementation of integrated care.

PubMed

Benzer, Justin K; Cramer, Irene E; Burgess, James F; Mohr, David C; Sullivan, Jennifer L; Charns, Martin P

2015-10-02

Integrating health care across specialized work units has the potential to lower costs and increase quality and access to mental health care. However, a key challenge for healthcare managers is how to develop policies, procedures, and practices that coordinate care across specialized units. The purpose of this study was to identify how organizational factors impacted coordination, and how to facilitate implementation of integrated care. Semi-structured interviews were conducted in August 2009 with 30 clinic leaders and 35 frontline staff who were recruited from a convenience sample of 16 primary care and mental health clinics across eight medical centers. Data were drawn from a management evaluation of primary care-mental health integration in the US Department of Veterans Affairs. To protect informant confidentiality, the institutional review board did not allow quotations. Interviews identified antecedents of organizational coordination processes, and highlighted how these antecedents can impact the implementation of integrated care. Overall, implementing new workflow practices were reported to create conflicts with pre-existing standardized coordination processes. Personal coordination (i.e., interpersonal communication processes) between primary care leaders and staff was reported to be effective in overcoming these barriers both by working around standardized coordination barriers and modifying standardized procedures. This study identifies challenges to integrated care that might be solved with attention to personal and standardized coordination. A key finding was that personal coordination both between primary care and mental health leaders and between frontline staff is important for resolving barriers related to integrated care implementation. Integrated care interventions can involve both new standardized procedures and adjustments to existing procedures. Aligning and integrating procedures between primary care and specialty care requires personal coordination amongst leaders. Interpersonal relationships should be strengthened between staff when personal connections are important for coordinating patient care across clinical settings.

Doctors' opinions on clinical coordination between primary and secondary care in the Catalan healthcare system.

PubMed

Aller, Marta-Beatriz; Vargas, Ingrid; Coderch, Jordi; Calero, Sebastià; Cots, Francesc; Abizanda, Mercè; Colomés, Lluís; Farré, Joan; Vázquez-Navarrete, María-Luisa

2017-08-26

To analyse doctors' opinions on clinical coordination between primary and secondary care in different healthcare networks and on the factors influencing it. A qualitative descriptive-interpretative study was conducted, based on semi-structured interviews. A two-stage theoretical sample was designed: 1) healthcare networks with different management models; 2) primary care and secondary care doctors in each network. Final sample size (n = 50) was reached by saturation. A thematic content analysis was conducted. In all networks doctors perceived that primary and secondary care given to patients was coordinated in terms of information transfer, consistency and accessibility to SC following a referral. However, some problems emerged, related to difficulties in acceding non-urgent secondary care changes in prescriptions and the inadequacy of some referrals across care levels. Doctors identified the following factors: 1) organizational influencing factors: coordination is facilitated by mechanisms that facilitate information transfer, communication, rapid access and physical proximity that fosters positive attitudes towards collaboration; coordination is hindered by the insufficient time to use mechanisms, unshared incentives in prescription and, in two networks, the change in the organizational model; 2) professional factors: clinical skills and attitudes towards coordination. Although doctors perceive that primary and secondary care is coordinated, they also highlighted problems. Identified factors offer valuable insights on where to direct organizational efforts to improve coordination. Copyright © 2017. Publicado por Elsevier España, S.L.U.

Relationship among team dynamics, care coordination and perception of safety culture in primary care.

PubMed

Blumenthal, Karen J; Chien, Alyna T; Singer, Sara J

2018-05-18

There remains a need to improve patient safety in primary care settings. Studies have demonstrated that creating high-performing teams can improve patient safety and encourage a safety culture within hospital settings, but little is known about this relationship in primary care. To examine how team dynamics relate to perceptions of safety culture in primary care and whether care coordination plays an intermediating role. This is a cross-sectional survey study with 63% response (n = 1082). The study participants were attending clinicians, resident physicians and other staff who interacted with patients from 19 primary care practices affiliated with Harvard Medical School. Three domains corresponding with our main measures: team dynamics, care coordination and safety culture. All items were measured on a 5-point Likert scale. We used linear regression clustered by practice site to assess the relationship between team dynamics and perceptions of safety culture. We also performed a mediation analysis to determine the extent to which care coordination explains the relationship between perceptions of team dynamics and of safety culture. For every 1-point increase in overall team dynamics, there was a 0.76-point increase in perception of safety culture [95% confidence interval (CI) 0.70-0.82, P < 0.001]. Care coordination mediated the relationship between team dynamics and the perception of safety culture. Our findings suggest there is a relationship between team dynamics, care coordination and perceptions of patient safety in a primary care setting. To make patients safer, we may need to pay more attention to how primary care providers work together to coordinate care.

Collaboration, Communication and Co-ordination in Agile Software Development Practice

NASA Astrophysics Data System (ADS)

Robinson, Hugh; Sharp, Helen

This chapter analyses the results of a series of observational studies of agile software developmentagile software development teams, identifying commonalities in collaboration, co-ordination and communication activities. Pairing and customer collaborationcustomer collaboration are focussed on to illustrate the nature of collaboration and communication, as are two simple physical artefacts that emerged through analysis as being an information-rich focal point for the co-ordination of collaboration and communication activities. The analysis shows that pairingpairing has common characteristics across all teams, while customer collaboration differs between the teams depending on the application and organisational context of development.

Immunohistochemical and ultrastructural characteristics of interstitial cells of Cajal in the rabbit duodenum. Presence of a single cilium

PubMed Central

Junquera, Concepción; Martínez-Ciriano, Carmen; Castiella, Tomás; Serrano, Pedro; Azanza, María Jesús; Ramón y Cajal Junquera, Santiago

2007-01-01

Abstract Santiago Ramón y Cajal discovered a new type of cell related to the myenteric plexus and also to the smooth muscle cells of the circular muscle layer of the intestine. Based on their morphology, relationships and staining characteristics, he considered these cells as primitive neurons. One century later, despite major improvements in cell biology, the interstitial cells of Cajal (ICCs) are still controversial for many researchers. The aim of study was to perform an immunohistochemical and ultrastructural characterization of the ICCs in the rabbit duo-denum. We have found interstitial cells that are positive for c-Kit, CD34 and nestin and are also positive for Ki67 protein, tightly associated with somatic cell proliferation. By means of electron microscopy, we describe ICCs around enteric ganglia. They present triangular or spindle forms and a very voluminous nucleus with scarce per-inuclear chromatin surrounded by a thin perinuclear cytoplasm that expands with long cytoplasmic processes. ICC processes penetrate among the smooth muscle cells and couple with the processes of other ICCs located in the connective tissue of the circular muscle layer and establish a three-dimensional network. Intercellular con-tacts by means of gap-like junctions are frequent. ICCs also establish gap-like junctions with smooth muscle cells. We also observe a population of interstitial cells of stellate morphology in the connective tissue that sur-rounds the muscle bundles in the circular muscle layer, usually close to nervous trunks. These cells establish different types of contacts with the muscle cells around them. In addition, the presence of a single cilium show-ing a structure 9 + 0 in an ICC is demonstrated for the first time. In conclusion, we report positive staining c-kit, CD34, nestin and Ki 67. ICCs fulfilled the usual transmission electron microscopy (TEM) criteria. A new ultrastructural characteristic of at least some ICCs is demonstrated: the presence of a single cilium. Some populations of ICCs in the rabbit duodenum present certain immunohistochemical and ultrastructural characteristics that often are present in progenitor cells. PMID:17760839

A novel zf-MYND protein, CHB-3, mediates guanylyl cyclase localization to sensory cilia and controls body size of Caenorhabditis elegans.

PubMed

Fujiwara, Manabi; Teramoto, Takayuki; Ishihara, Takeshi; Ohshima, Yasumi; McIntire, Steven L

2010-11-24

Cilia are important sensory organelles, which are thought to be essential regulators of numerous signaling pathways. In Caenorhabditis elegans, defects in sensory cilium formation result in a small-body phenotype, suggesting the role of sensory cilia in body size determination. Previous analyses suggest that lack of normal cilia causes the small-body phenotype through the activation of a signaling pathway which consists of the EGL-4 cGMP-dependent protein kinase and the GCY-12 receptor-type guanylyl cyclase. By genetic suppressor screening of the small-body phenotype of a cilium defective mutant, we identified a chb-3 gene. Genetic analyses placed chb-3 in the same pathway as egl-4 and gcy-12 and upstream of egl-4. chb-3 encodes a novel protein, with a zf-MYND motif and ankyrin repeats, that is highly conserved from worm to human. In chb-3 mutants, GCY-12 guanylyl cyclase visualized by tagged GFP (GCY-12::GFP) fails to localize to sensory cilia properly and accumulates in cell bodies. Our analyses suggest that decreased GCY-12 levels in the cilia of chb-3 mutants may cause the suppression of the small-body phenotype of a cilium defective mutant. By observing the transport of GCY-12::GFP particles along the dendrites to the cilia in sensory neurons, we found that the velocities and the frequencies of the particle movement are decreased in chb-3 mutant animals. How membrane proteins are trafficked to cilia has been the focus of extensive studies in vertebrates and invertebrates, although only a few of the relevant proteins have been identified. Our study defines a new regulator, CHB-3, in the trafficking process and also shows the importance of ciliary targeting of the signaling molecule, GCY-12, in sensory-dependent body size regulation in C. elegans. Given that CHB-3 is highly conserved in mammal, a similar system may be used in the trafficking of signaling proteins to the cilia of other species.

Challenges to Effective Primary Care-Specialty Communication and Coordination in the Mental Health Referral and Care Process for Publicly Insured Children.

PubMed

Porras-Javier, Lorena; Bromley, Elizabeth; Lopez, Maria; Coker, Tumaini R

2018-03-26

Publicly insured children needing referral to mental health (MH) services often do not access or receive services. The objective of this study was to identify gaps in communication and coordination between primary care providers (PCPs) and MH providers during the MH referral and care process for publicly insured children. Thirteen semi-structured interviews were conducted with 10 PCPs and staff from a federally qualified health center (FQHC) and 6 MH providers and staff from two local MH clinics. Interview participants identified multiple gaps in communication throughout the care process and different phases as priorities for improvement. PCPs described primary care-MH communication challenges during early phases, while MH providers described coordination challenges in transferring patients back to primary care for ongoing mental health management. Strategies are needed to improve primary care-specialty MH communication and coordination throughout all phases of the referral and care process, particularly at initial referral and transfer back to primary care.

PEG attachment to osteoblasts enhances mechanosensitivity.

PubMed

Hamamura, Kazunori; Weng, Yiming; Zhao, Jun; Yokota, Hiroki; Xie, Dong

2008-06-01

Fluid flow induces proliferation and differentiation of osteoblasts, and fibrous structure like a primary cilium on a cell surface contributes to flow sensing and flow-driven gene regulation. We address a question: Does attachment of synthetic polymers on a cell surface enhance mechanosensitivity of osteoblasts? Using MC3T3 osteoblast cells (C4 clone) and a PEG polymer, one of whose termini was covalently linked to a succinimidyl succinate group (functionalized PEG-PEGSS), we examined attachment of PEGSS to osteoblasts and evaluated its effects on the mRNA expression of stress-responsive genes. AFM images exhibited globular PEGSS conformation of approximately 100 nm in size, and SEM images confirmed the attachment of a cluster of pancake-like PEGSS molecules on the osteoblast surface. Compared to control cells incubated with unfunctionalized PEG, real-time PCR revealed that RNA upregulation of c-fos, egr1, ATF3 and Cox2 genes was magnified in the cells incubated with PEGSS. These results support a PEG-induced increase in mechanosensitivity of osteoblasts and indicate that the described approach would be useful to accelerate growth and development of osteoblasts for bone repair and tissue engineering.

INPP5E Preserves Genomic Stability through Regulation of Mitosis.

PubMed

Sierra Potchanant, Elizabeth A; Cerabona, Donna; Sater, Zahi Abdul; He, Ying; Sun, Zejin; Gehlhausen, Jeff; Nalepa, Grzegorz

2017-03-15

The partially understood phosphoinositide signaling cascade regulates multiple aspects of cellular metabolism. Previous studies revealed that INPP5E, the inositol polyphosphate-5-phosphatase that is mutated in the developmental disorders Joubert and MORM syndromes, is essential for the function of the primary cilium and maintenance of phosphoinositide balance in nondividing cells. Here, we report that INPP5E further contributes to cellular homeostasis by regulating cell division. We found that silencing or genetic knockout of INPP5E in human and murine cells impairs the spindle assembly checkpoint, centrosome and spindle function, and maintenance of chromosomal integrity. Consistent with a cell cycle regulatory role, we found that INPP5E expression is cell cycle dependent, peaking at mitotic entry. INPP5E localizes to centrosomes, chromosomes, and kinetochores in early mitosis and shuttles to the midzone spindle at mitotic exit. Our findings identify the previously unknown, essential role of INPP5E in mitosis and prevention of aneuploidy, providing a new perspective on the function of this phosphoinositide phosphatase in health and development. Copyright © 2017 Sierra Potchanant et al.

Functional genome-wide siRNA screen identifies KIAA0586 as mutated in Joubert syndrome

PubMed Central

Roosing, Susanne; Hofree, Matan; Kim, Sehyun; Scott, Eric; Copeland, Brett; Romani, Marta; Silhavy, Jennifer L; Rosti, Rasim O; Schroth, Jana; Mazza, Tommaso; Miccinilli, Elide; Zaki, Maha S; Swoboda, Kathryn J; Milisa-Drautz, Joanne; Dobyns, William B; Mikati, Mohamed A; İncecik, Faruk; Azam, Matloob; Borgatti, Renato; Romaniello, Romina; Boustany, Rose-Mary; Clericuzio, Carol L; D'Arrigo, Stefano; Strømme, Petter; Boltshauser, Eugen; Stanzial, Franco; Mirabelli-Badenier, Marisol; Moroni, Isabella; Bertini, Enrico; Emma, Francesco; Steinlin, Maja; Hildebrandt, Friedhelm; Johnson, Colin A; Freilinger, Michael; Vaux, Keith K; Gabriel, Stacey B; Aza-Blanc, Pedro; Heynen-Genel, Susanne; Ideker, Trey; Dynlacht, Brian D; Lee, Ji Eun; Valente, Enza Maria; Kim, Joon; Gleeson, Joseph G

2015-01-01

Defective primary ciliogenesis or cilium stability forms the basis of human ciliopathies, including Joubert syndrome (JS), with defective cerebellar vermis development. We performed a high-content genome-wide small interfering RNA (siRNA) screen to identify genes regulating ciliogenesis as candidates for JS. We analyzed results with a supervised-learning approach, using SYSCILIA gold standard, Cildb3.0, a centriole siRNA screen and the GTex project, identifying 591 likely candidates. Intersection of this data with whole exome results from 145 individuals with unexplained JS identified six families with predominantly compound heterozygous mutations in KIAA0586. A c.428del base deletion in 0.1% of the general population was found in trans with a second mutation in an additional set of 9 of 163 unexplained JS patients. KIAA0586 is an orthologue of chick Talpid3, required for ciliogenesis and Sonic hedgehog signaling. Our results uncover a relatively high frequency cause for JS and contribute a list of candidates for future gene discoveries in ciliopathies. DOI: http://dx.doi.org/10.7554/eLife.06602.001 PMID:26026149

Mutations in the inositol polyphosphate-5-phosphatase E gene link phosphatidyl inositol signaling to the ciliopathies

PubMed Central

Bielas, Stephanie L.; Silhavy, Jennifer L.; Brancati, Francesco; Kisseleva, Marina V.; Al-Gazali, Lihadh; Sztriha, Laszlo; Bayoumi, Riad A.; Zaki, Maha S.; Abdel-Aleem, Alice; Rosti, Ozgur; Kayserili, Hulya; Swistun, Dominika; Scott, Lesley C.; Bertini, Enrico; Boltshauser, Eugen; Fazzi, Elisa; Travaglini, Lorena; Field, Seth J.; Gayral, Stephanie; Jacoby, Monique; Schurmans, Stephane; Dallapiccola, Bruno; Majerus, Philip W.; Valente, Enza Maria; Gleeson, Joseph G.

2009-01-01

Phosphotidylinositol (PtdIns) signaling is tightly regulated, both spatially and temporally, by subcellularly localized PtdIns kinases and phosphatases that dynamically alter downstream signaling events 1. Joubert Syndrome (JS) characterized by a specific midbrain-hindbrain malformation (“molar tooth sign”) and variably associated retinal dystrophy, nephronophthisis, liver fibrosis and polydactyly 2, and is included in the newly emerging group of “ciliopathies”. In patients linking to JBTS1, we identified mutations in the INPP5E gene, encoding inositol polyphosphate-5-phosphatase E, which hydrolyzes the 5-phosphate of PtdIns(3,4,5)P3 and PtdIns(4,5)P2. Mutations clustered in the phosphatase domain and impaired 5-phosphatase activity, resulting in altered cellular PtdIns ratios. INPP5E localized to cilia in major organs affected in JS, and mutations promoted premature destabilization of cilia in response to stimulation. Thus, these data links PtdIns signaling to the primary cilium, a cellular structure that is becoming increasingly appreciated for its role in mediating cell signals and neuronal function. PMID:19668216

Intraflagellar transport 88 (IFT88) is crucial for craniofacial development in mice and is a candidate gene for human cleft lip and palate.

PubMed

Tian, Hua; Feng, Jifan; Li, Jingyuan; Ho, Thach-Vu; Yuan, Yuan; Liu, Yang; Brindopke, Frederick; Figueiredo, Jane C; Magee, William; Sanchez-Lara, Pedro A; Chai, Yang

2017-03-01

Ciliopathies are pleiotropic human diseases resulting from defects of the primary cilium, and these patients often have cleft lip and palate. IFT88 is required for the assembly and function of the primary cilia, which mediate the activity of key developmental signaling pathways. Through whole exome sequencing of a family of three affected siblings with isolated cleft lip and palate, we discovered that they share a novel missense mutation in IFT88 (c.915G > C, p.E305D), suggesting this gene should be considered a candidate for isolated orofacial clefting. In order to evaluate the function of IFT88 in regulating craniofacial development, we generated Wnt1-Cre;Ift88fl/fl mice to eliminate Ift88 specifically in cranial neural crest (CNC) cells. Wnt1-Cre;Ift88fl/flpups died at birth due to severe craniofacial defects including bilateral cleft lip and palate and tongue agenesis, following the loss of the primary cilia in the CNC-derived palatal mesenchyme. Loss of Ift88 also resulted in a decrease in neural crest cell proliferation during early stages of palatogenesis as well as a downregulation of the Shh signaling pathway in the palatal mesenchyme. Importantly, Osr2KI-Cre;Ift88fl/flmice, in which Ift88 is lost specifically in the palatal mesenchyme, exhibit isolated cleft palate. Taken together, our results demonstrate that IFT88 has a highly conserved function within the primary cilia of the CNC-derived mesenchyme in the lip and palate region in mice and is a strong candidate as an orofacial clefting gene in humans. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Team dynamics, clinical work satisfaction, and patient care coordination between primary care providers: A mixed methods study.

PubMed

Song, Hummy; Ryan, Molly; Tendulkar, Shalini; Fisher, Josephine; Martin, Julia; Peters, Antoinette S; Frolkis, Joseph P; Rosenthal, Meredith B; Chien, Alyna T; Singer, Sara J

Team-based care is essential for delivering high-quality, comprehensive, and coordinated care. Despite considerable research about the effects of team-based care on patient outcomes, few studies have examined how team dynamics relate to provider outcomes. The aim of this study was to examine relationships among team dynamics, primary care provider (PCP) clinical work satisfaction, and patient care coordination between PCPs in 18 Harvard-affiliated primary care practices participating in Harvard's Academic Innovations Collaborative. First, we administered a cross-sectional survey to all 548 PCPs (267 attending clinicians, 281 resident physicians) working at participating practices; 65% responded. We assessed the relationship of team dynamics with PCPs' clinical work satisfaction and perception of patient care coordination between PCPs, respectively, and the potential mediating effect of patient care coordination on the relationship between team dynamics and work satisfaction. In addition, we embedded a qualitative evaluation within the quantitative evaluation to achieve a convergent mixed methods design to help us better understand our findings and illuminate relationships among key variables. Better team dynamics were positively associated with clinical work satisfaction and quality of patient care coordination between PCPs. Coordination partially mediated the relationship between team dynamics and satisfaction for attending clinicians, suggesting that higher satisfaction depends, in part, on better teamwork, yielding more coordinated patient care. We found no mediating effects for resident physicians. Qualitative results suggest that sources of satisfaction from positive team dynamics for PCPs may be most relevant to attending clinicians. Improving primary care team dynamics could improve clinical work satisfaction among PCPs and patient care coordination between PCPs. In addition to improving outcomes that directly concern health care providers, efforts to improve aspects of team dynamics may also help resolve critical challenges in workforce planning in primary care.

The hedgehog system machinery controls transforming growth factor-β-dependent myofibroblastic differentiation in humans: involvement in idiopathic pulmonary fibrosis.

PubMed

Cigna, Natacha; Farrokhi Moshai, Elika; Brayer, Stéphanie; Marchal-Somme, Joëlle; Wémeau-Stervinou, Lidwine; Fabre, Aurélie; Mal, Hervé; Lesèche, Guy; Dehoux, Monique; Soler, Paul; Crestani, Bruno; Mailleux, Arnaud A

2012-12-01

Idiopathic pulmonary fibrosis (IPF) is a devastating disease of unknown cause. Key signaling developmental pathways are aberrantly expressed in IPF. The hedgehog pathway plays a key role during fetal lung development and may be involved in lung fibrogenesis. We determined the expression pattern of several Sonic hedgehog (SHH) pathway members in normal and IPF human lung biopsies and primary fibroblasts. The effect of hedgehog pathway inhibition was assayed by lung fibroblast proliferation and differentiation with and without transforming growth factor (TGF)-β1. We showed that the hedgehog pathway was reactivated in the IPF lung. Importantly, we deciphered the cross talk between the hedgehog and TGF-β pathway in human lung fibroblasts. TGF-β1 modulated the expression of key components of the hedgehog pathway independent of Smoothened, the obligatory signal transducer of the pathway. Smoothened was required for TGF-β1-induced myofibroblastic differentiation of control fibroblasts, but differentiation of IPF fibroblasts was partially resistant to Smoothened inhibition. Furthermore, functional hedgehog pathway machinery from the primary cilium, as well as GLI-dependent transcription in the nucleus, was required for the TGF-β1 effects on normal and IPF fibroblasts during myofibroblastic differentiation. These data identify the GLI transcription factors as potential therapeutic targets in lung fibrosis. Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Relational coordination between community health nurses and other professionals in delivering care to community-dwelling frail people.

PubMed

Cramm, Jane Murray; Hoeijmakers, Marjan; Nieboer, Anna Petra

2014-03-01

The first aim of this study was to investigate whether relational coordination is higher between primary care professionals and community health nurses than among other professionals. The second aim of this study was to investigate the relationship between different levels of relational coordination and primary care professionals' satisfaction with the care delivery of community health nurses. Community health nursing is based on the notion that all activities should respond to frail people's needs in a coordinated way, together with other professionals. Relational coordination is therefore important for the effective health-care delivery by these nurses. This cross-sectional study was performed among 167 professionals (n = 323, response rate 52%) who regularly worked with community health nurses. The results showed a higher degree of relational coordination with community health nurses than with other primary care professionals. Multilevel analyses revealed that professionals' satisfaction with the care delivered by community health nurses was influenced positively by relational coordination. Enhancing relational coordination between community health nurses and other primary care professionals in the neighborhood may improve the delivery of care to community-dwelling frail people. Comprehensive care delivery to community-dwelling frail people requires strong connections between all health and social care professionals. Community health nurses may be an important factor in strengthening these connections. © 2013 John Wiley & Sons Ltd.

Drosophila Ana1 is required for centrosome assembly and centriole elongation.

PubMed

Saurya, Saroj; Roque, Hélio; Novak, Zsofia A; Wainman, Alan; Aydogan, Mustafa G; Volanakis, Adam; Sieber, Boris; Pinto, David Miguel Susano; Raff, Jordan W

2016-07-01

Centrioles organise centrosomes and cilia, and these organelles have an important role in many cell processes. In flies, the centriole protein Ana1 is required for the assembly of functional centrosomes and cilia. It has recently been shown that Cep135 (also known as Bld10) initially recruits Ana1 to newly formed centrioles, and that Ana1 then recruits Asl (known as Cep152 in mammals) to promote the conversion of these centrioles into centrosomes. Here, we show that ana1 mutants lack detectable centrosomes in vivo, that Ana1 is irreversibly incorporated into centrioles during their assembly and appears to play a more important role in maintaining Asl at centrioles than in initially recruiting Asl to centrioles. Unexpectedly, we also find that Ana1 promotes centriole elongation in a dose-dependent manner: centrioles are shorter when Ana1 dosage is reduced and are longer when Ana1 is overexpressed. This latter function of Ana1 appears to be distinct from its role in centrosome and cilium function, as a GFP-Ana1 fusion lacking the N-terminal 639 amino acids of the protein can support centrosome assembly and cilium function but cannot promote centriole over-elongation when overexpressed. © 2016. Published by The Company of Biologists Ltd.

Chloral hydrate alters the organization of the ciliary basal apparatus and cell organelles in sea urchin embryos

NASA Technical Reports Server (NTRS)

Chakrabarti, A.; Schatten, H.; Mitchell, K. D.; Crosser, M.; Taylor, M.

1998-01-01

The mitotic inhibitor, chloral hydrate, induces ciliary loss in the early embryo phase of Lytechinus pictus. It causes a breakdown of cilia at the junction of the cilium and the basal body known as the basal plate. This leaves the plasma membrane temporarily unsealed. The basal apparatus accessory structures, consisting of the basal body, basal foot, basal foot cap, striated side arm, and striated rootlet, are either misaligned or disintegrated by treatment with chloral hydrate. Furthermore, microtubules which are associated with the basal apparatus are disassembled. Mitochondria accumulate at the base of cilia - underneath the plasma membrane - and show alterations in their structural organization. The accumulation of mitochondria is observed in 40% of all electron micrograph sections while 60% show the areas mostly devoid of mitochondria. The microvilli surrounding a cilium and striated rootlet remain intact in the presence of chloral hydrate. These results suggest that deciliation in early sea urchin embryos by chloral hydrate is caused by combined effects on the ciliary membrane and on microtubules in the cilia. Furthermore, it is suggested that chloral hydrate can serve as a tool to explore the cytoskeletal mechanisms that are involved in cilia motility in the developing sea urchin embryo.

Reduced primary cilia length and altered Arl13b expression are associated with deregulated chondrocyte Hedgehog signaling in alkaptonuria

PubMed Central

Thorpe, Stephen D.; Gambassi, Silvia; Thompson, Clare L.; Chandrakumar, Charmilie

2017-01-01

Alkaptonuria (AKU) is a rare inherited disease resulting from a deficiency of the enzyme homogentisate 1,2‐dioxygenase which leads to the accumulation of homogentisic acid (HGA). AKU is characterized by severe cartilage degeneration, similar to that observed in osteoarthritis. Previous studies suggest that AKU is associated with alterations in cytoskeletal organization which could modulate primary cilia structure/function. This study investigated whether AKU is associated with changes in chondrocyte primary cilia and associated Hedgehog signaling which mediates cartilage degradation in osteoarthritis. Human articular chondrocytes were obtained from healthy and AKU donors. Additionally, healthy chondrocytes were treated with HGA to replicate AKU pathology (+HGA). Diseased cells exhibited shorter cilia with length reductions of 36% and 16% in AKU and +HGA chondrocytes respectively, when compared to healthy controls. Both AKU and +HGA chondrocytes demonstrated disruption of the usual cilia length regulation by actin contractility. Furthermore, the proportion of cilia with axoneme breaks and bulbous tips was increased in AKU chondrocytes consistent with defective regulation of ciliary trafficking. Distribution of the Hedgehog‐related protein Arl13b along the ciliary axoneme was altered such that its localization was increased at the distal tip in AKU and +HGA chondrocytes. These changes in cilia structure/trafficking in AKU and +HGA chondrocytes were associated with a complete inability to activate Hedgehog signaling in response to exogenous ligand. Thus, we suggest that altered responsiveness to Hedgehog, as a consequence of cilia dysfunction, may be a contributing factor in the development of arthropathy highlighting the cilium as a novel target in AKU. PMID:28158906

Moving survivorship care plans forward: focus on care coordination.

PubMed

Salz, Talya; Baxi, Shrujal

2016-07-01

After completing treatment for cancer, the coordination of oncology and primary care presents a challenge for cancer survivors. Many survivors need continued oncology follow-up, and all survivors require primary care. Coordinating the shared care of a cancer survivor, or facilitating an informed handoff from oncology to primary care, is essential for cancer survivors. Survivorship care plans are personalized documents that summarize cancer treatment and outline a plan of recommended ongoing care, with the goal of facilitating the coordination of post-treatment care. Despite their face validity, five trials have failed to demonstrate the effectiveness of survivorship care plans. We posit that these existing trials have critical shortcomings and do not adequately address whether survivorship care plans improve care coordination. Moving forward, we propose four criteria for future trials of survivorship care plans: focusing on high-needs survivor populations, tailoring the survivorship care plan to the care setting, facilitating implementation of the survivorship care plan in clinical practice, and selecting appropriate trial outcomes to assess care coordination. When trials meet these criteria, we can finally assess whether survivorship care plans help cancer survivors receive optimal oncology and primary care. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Care Coordination for Youth With Mental Health Disorders in Primary Care.

PubMed

Hobbs Knutson, Katherine; Meyer, Mark J; Thakrar, Nisha; Stein, Bradley D

2018-01-01

Many children are treated for mental health disorders in primary care settings. The system of care (SOC) provides a framework for collaboration among pediatric mental health providers, but it is unclear if youth treated for mental health disorders in primary care receive such coordination. At the South Boston Community Health Center from September /2012 to August 2013 for 74 individuals ≤18 years, the odds of contact with SOC agencies (mental health, education, child protective services, juvenile justice and developmental disabilities) were compared for mental health treatment in primary versus specialty care. The odds of SOC contact within primary care were lower compared to specialty care (OR = 0.43, 95% CI = 0.29-0.66), specifically for mental health (OR = 0.54, 95% CI = 0.25-1.2), education (OR = 0.12, 95% CI = 0.050-0.28), and child protective services (OR = 0.64, 95% CI = 0.22-1.9). As care coordination may improve health outcomes, increased support and education for care coordination specific to youth treated for mental health disorders in primary care settings may be warranted.

The flagellum of Trypanosoma brucei: new tricks from an old dog

PubMed Central

Ralston, Katherine S.; Hill, Kent L.

2010-01-01

African trypanosomes, i.e. Trypanosoma brucei and related sub-species, are devastating human and animal pathogens that cause significant human mortality and limit sustained economic development in sub-Saharan Africa. Trypanosoma brucei is a highly motile protozoan parasite and coordinated motility is central to both disease pathogenesis in the mammalian host and parasite development in the tsetse fly vector. Since motility is critical for parasite development and pathogenesis, understanding unique aspects of the T. brucei flagellum may uncover novel targets for therapeutic intervention in African sleeping sickness. Moreover, studies of conserved features of the T. brucei flagellum are directly relevant to understanding fundamental aspects of flagellum and cilium function in other eukaryotes, making T. brucei an important model system. The T. brucei flagellum contains a canonical 9 + 2 axoneme, together with additional features that are unique to kinetoplastids and a few closely-related organisms. Until recently, much of our knowledge of the structure and function of the trypanosome flagellum was based on analogy and inference from other organisms. There has been an explosion in functional studies in T. brucei in recent years, revealing conserved as well as novel and unexpected structural and functional features of the flagellum. Most notably, the flagellum has been found to be an essential organelle, with critical roles in parasite motility, morphogenesis, cell division and immune evasion. This review highlights recent discoveries on the T. brucei flagellum. PMID:18472102

Integrated primary health care in Australia.

PubMed

Davies, Gawaine Powell; Perkins, David; McDonald, Julie; Williams, Anna

2009-10-14

To fulfil its role of coordinating health care, primary health care needs to be well integrated, internally and with other health and related services. In Australia, primary health care services are divided between public and private sectors, are responsible to different levels of government and work under a variety of funding arrangements, with no overarching policy to provide a common frame of reference for their activities. Over the past decade, coordination of service provision has been improved by changes to the funding of private medical and allied health services for chronic conditions, by the development in some states of voluntary networks of services and by local initiatives, although these have had little impact on coordination of planning. Integrated primary health care centres are being established nationally and in some states, but these are too recent for their impact to be assessed. Reforms being considered by the federal government include bringing primary health care under one level of government with a national primary health care policy, establishing regional organisations to coordinate health planning, trialling voluntary registration of patients with general practices and reforming funding systems. If adopted, these could greatly improve integration within primary health care. Careful change management and realistic expectations will be needed. Also other challenges remain, in particular the need for developing a more population and community oriented primary health care.

The Music Co-ordinator in the Primary School

ERIC Educational Resources Information Center

Button, Stuart; Potter, Allison

2006-01-01

This article reports on the results of a study which investigated teachers' and head teachers' perceptions of the role of the music co-ordinator in the primary school, and provides insight into how the role might be made more effective. The teachers participating in this project were chosen from twenty primary schools from one local educational…

Development and validation of the Medical Home Care Coordination Survey for assessing care coordination in the primary care setting from the patient and provider perspectives.

PubMed

Zlateva, Ianita; Anderson, Daren; Coman, Emil; Khatri, Khushbu; Tian, Terrence; Fifield, Judith

2015-06-07

Community health centers are increasingly embracing the Patient Centered Medical Home (PCMH) model to improve quality, access to care, and patient experience while reducing healthcare costs. Care coordination (CC) is an important element of the PCMH model, but implementation and measurability of CC remains a problem within the outpatient setting. Assessing CC is an integral component of quality monitoring in health care systems. This study developed and validated the Medical Home Care Coordination Survey (MHCCS), to fill the gap in assessing CC in primary care from the perspectives of patients and their primary healthcare teams. We conducted a review of relevant literature and existing care coordination instruments identified by bibliographic search and contact with experts. After identifying all care coordination domains that could be assessed by primary healthcare team members and patients, we developed a conceptual model. Potentially appropriate items from existing published CC measures, along with newly developed items, were matched to each domain for inclusion. A modified Delphi approach was used to establish content validity. Primary survey data was collected from 232 patients with care transition and/or complex chronic illness needs from the Community Health Center, Inc. and from 164 staff members from 12 community health centers across the country via mail, phone and online survey. The MHCCS was validated for internal consistency, reliability, discriminant and convergent validity. This study was conducted at the Community Health Center, Inc. from January 15, 2012 to July 15, 2014. The 13-item MHCCS - Patient and the 32-item MHCCS - Healthcare Team were developed and validated. Exploratory Structural Equation Modeling was used to test the hypothesized domain structure. Four CC domains were confirmed from the patient group and eight were confirmed from the primary healthcare team group. All domains had high reliability (Cronbach's α scores were above 0.8). Patients experience the ultimate output of care coordination services, but primary healthcare staff members are best primed to perceive many of the structural elements of care coordination. The proactive measurement and monitoring of the core domains from both perspectives provides a richer body of information for the continuous improvement of care coordination services. The MHCCS shows promise as a valid and reliable assessment of these CC efforts.

Coordination between primary and secondary care: the role of electronic messages and economic incentives.

PubMed

La Rocca, Antonella; Hoholm, Thomas

2017-02-17

In Norway, a government reform has recently been introduced to enhance coordination between primary and secondary care. This paper examines the effects of two newly introduced measures to improve the coordination: an ICT-based communication tool/standard and an economic incentive scheme. This qualitative study is based primarily on 27 open-ended interviews. We interviewed nine employees at a hospital (the focal actor), 17 employees from seven different municipalities, and a representative of a Regional Health Authority. ICT-based communication is perceived to facilitate information exchange between primary and secondary care, thus positively affecting coordination. However, the economic incentive scheme appears to have the opposite effect by creating tensions between the two organizations and accentuating power asymmetry in favor of secondary care. The inter-organizational nature of coordination in health care makes it crucial for policymakers and management of care organizations to conceive incentives and instruments that work jointly across organizations rather than at only one of the health care organizations involved. Such an approach is likely to favor a more symmetrical pattern of collaboration between primary and secondary care.

The importance of relational coordination and reciprocal learning for chronic illness care within primary care teams.

PubMed

Noël, Polly Hitchcock; Lanham, Holly J; Palmer, Ray F; Leykum, Luci K; Parchman, Michael L

2013-01-01

Recent research from a complexity theory perspective suggests that implementation of complex models of care, such as the Chronic Care Model (CCM), requires strong relationships and learning capacities among primary care teams. Our primary aim was to assess the extent to which practice member perceptions of relational coordination and reciprocal learning were associated with the presence of CCM elements in community-based primary care practices. We used baseline measures from a cluster randomized controlled trial testing a practice facilitation intervention to implement the CCM and improve risk factor control for patients with Type 2 diabetes in small primary care practices. Practice members (i.e., physicians, nonphysician providers, and staff) completed baseline assessments, which included the Relational Coordination Scale, Reciprocal Learning Scale, and the Assessment of Chronic Illness Care (ACIC) survey, along with items assessing individual and clinic characteristics. To assess the association between Relational Coordination, Reciprocal Learning, and ACIC, we used a series of hierarchical linear regression models accounting for clustering of individual practice members within clinics and controlling for individual- and practice-level characteristics and tested for mediation effects. A total of 283 practice members from 39 clinics completed baseline measures. Relational Coordination scores were significantly and positively associated with ACIC scores (Model 1). When Reciprocal Learning was added, Relational Coordination remained a significant yet notably attenuated predictor of ACIC (Model 2). The mediation effect was significant (z = 9.3, p < .01); 24% of the association between Relational Coordination and ACIC scores was explained by Reciprocal Learning. Of the individual- and practice-level covariates included in Model 3, only the presence of an electronic medical record was significant; Relational Coordination and Reciprocal Learning remained significant independent predictors of ACIC. Efforts to implement complex models of care should incorporate strategies to strengthen relational coordination and reciprocal learning among team members.

The Importance of Relational Coordination and Reciprocal Learning for Chronic Illness Care within Primary Care Teams

PubMed Central

Noël, Polly Hitchcock; Lanham, Holly J.; Palmer, Ray F.; Leykum, Luci K.; Parchman, Michael L.

2012-01-01

Background Recent research from a complexity theory perspective suggests that implementation of complex models of care, such as the Chronic Care Model (CCM), requires strong relationships and learning capacities among primary care teams. Purposes Our primary aim was to assess the extent to which practice member perceptions of relational coordination and reciprocal learning were associated with the presence of CCM elements in community-based primary care practices. Methodology/Approach We used baseline measures from a cluster randomized controlled trial testing a practice facilitation intervention to implement the CCM and improve risk factor control for patients with type 2 diabetes in small primary care practices. Practice members (i.e., physicians, non-physician providers, and staff) completed baseline assessments, which included the Relational Coordination Scale, Reciprocal Learning Scale, and the Assessment of Chronic Illness Care (ACIC) survey, along with items assessing individual and clinic characteristics. To assess the association between Relational Coordination, Reciprocal Learning, and ACIC, we used a series of hierarchical linear regression models accounting for clustering of individual practice members within clinics and controlling for individual- and practice-level characteristics, and tested for mediation effects. Findings 283 practice members from 39 clinics completed baseline measures. Relational Coordination scores were significantly and positively associated with ACIC scores (Model 1). When Reciprocal Learning was added, Relational Coordination remained a significant yet notably attenuated predictor of ACIC (Model 2). The mediation effect was significant (z = 9.3, p<.01); 24% of the association between Relational Coordination and ACIC scores was explained by Reciprocal Learning. Of the individual and practice level covariates included in Model 3, only the presence of an electronic medical record was significant; Relational Coordination and Reciprocal Learning remained significant independent predictors of ACIC. Practice Implications Efforts to implement complex models of care should incorporate strategies to strengthen relational coordination and reciprocal learning among team members. PMID:22310483

[Primary Health Care in the coordination of health care networks: an integrative review].

PubMed

Rodrigues, Ludmila Barbosa Bandeira; Silva, Patricia Costa Dos Santos; Peruhype, Rarianne Carvalho; Palha, Pedro Fredemir; Popolin, Marcela Paschoal; Crispim, Juliane de Almeida; Pinto, Ione Carvalho; Monroe, Aline Aparecida; Arcêncio, Ricardo Alexandre

2014-02-01

Health systems organized in health care networks and coordinated by Primary Health Care can contribute to an improvement in clinical quality with a positive impact on health outcomes and user satisfaction (by improving access and resolubility) and a reduction in the costs of local health systems. Thus, the scope of this paper is to analyze the scientific output about the evidence, potential, challenges and prospects of Primary Health Care in the coordination of Health Care Networks. To achieve this, the integrative review method was selected covering the period between 2000 and 2011. The databases selected were Medline (Medical Literature Analysis and Retrieval System online), Lilacs (Latin American Literature in Health Sciences) and SciELO (Scientific Electronic Library Online). Eighteen articles fulfilled the selection criteria. It was seen that the potential impacts of primary care services supersede the inherent weaknesses. However, the results revealed the need for research with a higher level of classification of the scientific evidence about the role of Primary Healh Care in the coordination of Health Care Networks.

How do women with chronic fatigue syndrome/myalgic encephalomyelitis rate quality and coordination of healthcare services? A cross-sectional study.

PubMed

Hansen, Anne Helen; Lian, Olaug S

2016-04-04

To test the association between self-rated health and self-rated degree of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME), and CFS/ME patients' assessment of quality of primary care, specialist care and coordination of care. Cross-sectional study. Self-reported questionnaire data from women members of The Norwegian ME Association obtained in 2013. 431 women with CFS/ME aged 16-73 years. The participants' assessment of quality in primary care, specialist care and in coordination of care (good/very good or poor/very poor). Main explanatory variables: self-rated health and self-rated degree of CFS/ME. Quality of care was rated poor by 60.6% in primary care, by 47.7% in specialist care, and by 71.2% regarding coordination of care. Poorer self-rated health increased the probability of rating quality in primary care poor, particularly among women 40 years and over (OR 2.38, 95% CI 1.63 to 3.49), women with university education (OR 2.57, CI 1.68 to 3.94), and owing to less frequent general practitioner (GP) visits (OR 2.46, CI 1.60 to 3.78). Poorer self-rated health increased the probability of rating quality poor in specialist care (OR 1.38, CI 1.05 to 1.82), but not in coordination of care. A more severe CFS/ME was associated with a higher probability of rating quality in primary care poor (OR 0.61, CI 0.38 to 0.93). Frequent visitors and those with a long GP relationship were less likely to report primary care quality as poor. A large proportion of women with CFS/ME rated quality of care poor/very poor in primary care, specialist care and in coordination of care. The dissatisfaction was higher for primary care than for specialist care. Overall, poorer self-rated health and a more severe CFS/ME were associated with lower quality scores in primary and specialist care, but not in coordination of care. Healthcare services, as assessed by women with CFS/ME, do have a large potential for improvement. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Enhancing the primary care team to provide redesigned care: the roles of practice facilitators and care managers.

PubMed

Taylor, Erin Fries; Machta, Rachel M; Meyers, David S; Genevro, Janice; Peikes, Deborah N

2013-01-01

Efforts to redesign primary care require multiple supports. Two potential members of the primary care team-practice facilitator and care manager-can play important but distinct roles in redesigning and improving care delivery. Facilitators, also known as quality improvement coaches, assist practices with coordinating their quality improvement activities and help build capacity for those activities-reflecting a systems-level approach to improving quality, safety, and implementation of evidence-based practices. Care managers provide direct patient care by coordinating care and helping patients navigate the system, improving access for patients, and communicating across the care team. These complementary roles aim to help primary care practices deliver coordinated, accessible, comprehensive, and patient-centered care.

Improving care coordination in primary care.

PubMed

Wagner, Edward H; Sandhu, Nirmala; Coleman, Katie; Phillips, Kathryn E; Sugarman, Jonathan R

2014-11-01

Although coordinating care is a defining characteristic of primary care, evidence suggests that both patients and providers perceive failures in communication and care when care is received from multiple sources. To examine the utility of a newly developed Care Coordination Model in improving care coordination among participating practices in the Safety Net Medical Home Initiative (SNMHI). In this paper, we used correlation analysis to evaluate whether application of the elements of the Care Coordination Model by SNMHI sites, as measured by the Key Activities Checklist (KAC), was associated with more effective care coordination as measured by another instrument, the PCMH-A. SNMHI measures are practice self-assessments based on the 8 change concepts that define a PCMH, one of which is Care Coordination. For this study, we correlated 12 KAC items that describe activities felt to improve coordination of care with 5 PCMH-A items that indicate the extent to which a practice has developed the capability to effectively coordinate care. Practice staff indicated whether any of the KAC activities were being test, implemented, sustained, or not on 4 occasions. The Care Coordination Model elements-assume accountability, build relationships with care partners, support patients through the referral or transition process, and create connections to support information exchange-were positively correlated with some PCMH-A care coordination items but not others. Activities related to the model were most strongly correlated with following up patients seen in the Emergency Department or discharged from hospital. The analysis provides suggestive evidence that activities consistent with the 4 elements of the Care Coordination Model may enable safety net primary care to better coordinate care for its patients, but further study is clearly needed.

Care Coordination Associated with Improved Timing of Newborn Primary Care Visits.

PubMed

Goyal, Neera K; Hall, Eric S; Kahn, Robert S; Wexelblatt, Scott L; Greenberg, James M; Samaan, Zeina M; Brown, Courtney M

2016-09-01

Objective Despite practice recommendations that all newborns be examined within 3-5 days after discharge, many are not seen within this timeframe. Our objective was to determine the association between care coordination and timing of newborn follow-up. Methods This retrospective study evaluated 6251 newborns from eight maternity hospitals who scheduled a primary care appointment at one of two academic pediatric practices over 3.5 years. Two programs were sequentially implemented: (1) newborn discharge coordination, and (2) primary care intake coordination. Primary outcome was days between discharge and follow-up, dichotomized as ≤ or >5 days. Number of rescheduled appointments and loss to follow-up were also assessed. Adjusted relative risks (RR) and odds ratios (OR) were determined by piecewise generalized linear and logistic regression. Results Among 5943 newborns with a completed visit, 52.9 % were seen within 5 days of discharge (mean 6.7 days). After multivariable adjustment, the pre-exposure period (8 months) demonstrated a downward monthly trend in completing early follow-up (RR 0.93, p < 0.001). After initial program implementation, we observed a 3 % monthly increase (RR 1.03, p < 0.001 for test of slope change from pre-exposure to post-exposure), such that likelihood of recommended follow-up increased by roughly 72 % after discharge coordinator implementation and roughly 33 % after primary care coordinator implementation. The latter was also associated with a 13 % monthly decrease in odds of loss to follow-up (OR 0.87, p < 0.001). Conclusions for Practice Care coordination increases adherence among low income families to recommended newborn follow-up after birth hospitalization.

Care coordination between specialty care and primary care: a focus group study of provider perspectives on strong practices and improvement opportunities

PubMed Central

Kim, Bo; Lucatorto, Michelle A; Hawthorne, Kara; Hersh, Janis; Myers, Raquel; Elwy, A Rani; Graham, Glenn D

2015-01-01

Care coordination between the specialty care provider (SCP) and the primary care provider (PCP) is a critical component of safe, efficient, and patient-centered care. Veterans Health Administration conducted a series of focus groups of providers, from specialty care and primary care clinics at VA Medical Centers nationally, to assess 1) what SCPs and PCPs perceive to be current practices that enable or hinder effective care coordination with one another and 2) how these perceptions differ between the two groups of providers. A qualitative thematic analysis of the gathered data validates previous studies that identify communication as being an important enabler of coordination, and uncovers relationship building between specialty care and primary care (particularly through both formal and informal relationship-building opportunities such as collaborative seminars and shared lunch space, respectively) to be the most notable facilitator of effective communication between the two sides. Results from this study suggest concrete next steps that medical facilities can take to improve care coordination, using as their basis the mutual understanding and respect developed between SCPs and PCPs through relationship-building efforts. PMID:25653538

Care coordination between specialty care and primary care: a focus group study of provider perspectives on strong practices and improvement opportunities.

PubMed

Kim, Bo; Lucatorto, Michelle A; Hawthorne, Kara; Hersh, Janis; Myers, Raquel; Elwy, A Rani; Graham, Glenn D

2015-01-01

Care coordination between the specialty care provider (SCP) and the primary care provider (PCP) is a critical component of safe, efficient, and patient-centered care. Veterans Health Administration conducted a series of focus groups of providers, from specialty care and primary care clinics at VA Medical Centers nationally, to assess 1) what SCPs and PCPs perceive to be current practices that enable or hinder effective care coordination with one another and 2) how these perceptions differ between the two groups of providers. A qualitative thematic analysis of the gathered data validates previous studies that identify communication as being an important enabler of coordination, and uncovers relationship building between specialty care and primary care (particularly through both formal and informal relationship-building opportunities such as collaborative seminars and shared lunch space, respectively) to be the most notable facilitator of effective communication between the two sides. Results from this study suggest concrete next steps that medical facilities can take to improve care coordination, using as their basis the mutual understanding and respect developed between SCPs and PCPs through relationship-building efforts.

Towards implementing coordinated healthy lifestyle promotion in primary care: a mixed method study.

PubMed

Thomas, Kristin; Bendtsen, Preben; Krevers, Barbro

2015-01-01

Primary care is increasingly being encouraged to integrate healthy lifestyle promotion in routine care. However, implementation has been suboptimal. Coordinated care could facilitate lifestyle promotion practice but more empirical knowledge is needed about the implementation process of coordinated care initiatives. This study aimed to evaluate the implementation of a coordinated healthy lifestyle promotion initiative in a primary care setting. A mixed method, convergent, parallel design was used. Three primary care centres took part in a two-year research project. Data collection methods included individual interviews, document data and questionnaires. The General Theory of Implementation was used as a framework in the analysis to integrate the data sources. Multi-disciplinary teams were implemented in the centres although the role of the teams as a resource for coordinated lifestyle promotion was not fully embedded at the centres. Embedding of the teams was challenged by differences among the staff, patients and team members on resources, commitment, social norms and roles. The study highlights the importance of identifying and engaging key stakeholders early in an implementation process. The findings showed how the development phase influenced the implementation and embedding processes, which add aspects to the General Theory of Implementation.

Chronic Fluid Flow Is an Environmental Modifier of Renal Epithelial Function

PubMed Central

Resnick, Andrew

2011-01-01

Although solitary or sensory cilia are present in most cells of the body and their existence has been known since the sixties, very little is been known about their functions. One suspected function is fluid flow sensing- physical bending of cilia produces an influx of Ca++, which can then result in a variety of activated signaling pathways. Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a progressive disease, typically appearing in the 5th decade of life and is one of the most common monogenetic inherited human diseases, affecting approximately 600,000 people in the United States. Because ADPKD is a slowly progressing disease, I asked how fluid flow may act, via the primary cilium, to alter epithelial physiology during the course of cell turnover. I performed an experiment to determine under what conditions fluid flow can result in a change of function of renal epithelial tissue. A wildtype epithelial cell line derived the cortical collecting duct of a heterozygous offspring of the Immortomouse (Charles River Laboratory) was selected as our model system. Gentle orbital shaking was used to induce physiologically relevant fluid flow, and periodic measurements of the transepithelial Sodium current were performed. At the conclusion of the experiment, mechanosensitive proteins of interest were visualized by immunostaining. I found that fluid flow, in itself, modifies the transepithelial sodium current, cell proliferation, and the actin cytoskeleton. These results significantly impact the understanding of both the mechanosensation function of primary cilia as well as the understanding of ADPKD disease progression. PMID:22046444

Tubby family proteins are adapters for ciliary trafficking of integral membrane proteins

PubMed Central

Shimada, Issei S.; Loriot, Evan

2017-01-01

The primary cilium is a paradigmatic organelle for studying compartmentalized signaling; however, unlike soluble protein trafficking, processes targeting integral membrane proteins to cilia are poorly understood. In this study, we determine that the tubby family protein TULP3 functions as a general adapter for ciliary trafficking of structurally diverse integral membrane cargo, including multiple reported and novel rhodopsin family G protein–coupled receptors (GPCRs) and the polycystic kidney disease–causing polycystin 1/2 complex. The founding tubby family member TUB also localizes to cilia similar to TULP3 and determines trafficking of a subset of these GPCRs to neuronal cilia. Using minimal ciliary localization sequences from GPCRs and fibrocystin (also implicated in polycystic kidney disease), we demonstrate these motifs to be sufficient and TULP3 dependent for ciliary trafficking. We propose a three-step model for TULP3/TUB-mediated ciliary trafficking, including the capture of diverse membrane cargo by the tubby domain in a phosphoinositide 4,5-bisphosphate (PI(4,5)P2)-dependent manner, ciliary delivery by intraflagellar transport complex A binding to the TULP3/TUB N terminus, and subsequent release into PI(4,5)P2-deficient ciliary membrane. PMID:28154160

hemingway is required for sperm flagella assembly and ciliary motility in Drosophila.

PubMed

Soulavie, Fabien; Piepenbrock, David; Thomas, Joëlle; Vieillard, Jennifer; Duteyrat, Jean-Luc; Cortier, Elisabeth; Laurençon, Anne; Göpfert, Martin C; Durand, Bénédicte

2014-04-01

Cilia play major functions in physiology and development, and ciliary dysfunctions are responsible for several diseases in humans called ciliopathies. Cilia motility is required for cell and fluid propulsion in organisms. In humans, cilia motility deficiencies lead to primary ciliary dyskinesia, with upper-airways recurrent infections, left-right asymmetry perturbations, and fertility defects. In Drosophila, we identified hemingway (hmw) as a novel component required for motile cilia function. hmw encodes a 604-amino acid protein characterized by a highly conserved coiled-coil domain also found in the human orthologue, KIAA1430. We show that HMW is conserved in species with motile cilia and that, in Drosophila, hmw is expressed in ciliated sensory neurons and spermatozoa. We created hmw-knockout flies and found that they are hearing impaired and male sterile. hmw is implicated in the motility of ciliated auditory sensory neurons and, in the testis, is required for elongation and maintenance of sperm flagella. Because HMW is absent from mature flagella, we propose that HMW is not a structural component of the motile axoneme but is required for proper acquisition of motile properties. This identifies HMW as a novel, evolutionarily conserved component necessary for motile cilium function and flagella assembly.

ARL2BP, a protein linked to Retinitis Pigmentosa, is needed for normal photoreceptor cilia doublets and outer segment structure.

PubMed

Moye, Abigail R; Singh, Ratnesh; Kimler, Victoria A; Dilan, Tanya L; Munezero, Daniella; Saravanan, Thamaraiselvi; Goldberg, Andrew F X; Ramamurthy, Visvanathan

2018-05-02

The outer segment (OS) of photoreceptor cells is an elaboration of a primary cilium with organized stacks of membranous discs that contain the proteins needed for phototransduction and vision. Though cilia formation and function has been well characterized, little is known about the role of cilia in the development of photoreceptor OS. Nevertheless, progress has been made by studying mutations in ciliary proteins which often result in malformed outer segments and lead to blinding diseases. To investigate how ciliary proteins contribute to outer segment formation, we generated a knockout mouse model for ARL2BP, a ciliary protein linked to Retinitis Pigmentosa. The knockout mice display an early and progressive reduction in visual response. Prior to photoreceptor degeneration we observed disorganization of the photoreceptor OS, with vertically aligned discs and shortened axonemes. Interestingly, ciliary doublet microtubule structure was also impaired, displaying open B-tubule doublets, paired with loss of singlet microtubules. Based on results from this study, we conclude that ARL2BP is necessary for photoreceptor cilia doublet formation and axoneme elongation, which is required for outer segment morphogenesis and vision.

Novel TMEM67 Mutations and Genotype-phenotype Correlates in Meckelin-related Ciliopathies

PubMed Central

Iannicelli, Miriam; Brancati, Francesco; Mougou-Zerelli, Soumaya; Mazzotta, Annalisa; Thomas, Sophie; Elkhartoufi, Nadia; Travaglini, Lorena; Gomes, Céline; Ardissino, Gian Luigi; Bertini, Enrico; Boltshauser, Eugen; Castorina, Pierangela; D'Arrigo, Stefano; Fischetto, Rita; Leroy, Brigitte; Loget, Philippe; Bonnière, Maryse; Starck, Lena; Tantau, Julia; Gentilin, Barbara; Majore, Silvia; Swistun, Dominika; Flori, Elizabeth; Lalatta, Faustina; Pantaleoni, Chiara; Johannes.Penzien; Grammatico, Paola; Dallapiccola, Bruno; Gleeson, Joseph G.; Attie-Bitach, Tania; Valente, Enza Maria

2010-01-01

Human ciliopathies are hereditary conditions caused by defects of proteins expressed at the primary cilium. Among ciliopathies, Joubert syndrome and related disorders (JSRD), Meckel syndrome (MKS) and nephronophthisis (NPH) present clinical and genetic overlap, being allelic at several loci. One of the most interesting gene is TMEM67, encoding the transmembrane protein meckelin. We performed mutation analysis of TMEM67 in 341 probands, including 265 JSRD representative of all clinical subgroups and 76 MKS fetuses. We identified 33 distinct mutations, of which 20 were novel, in 8/10 (80%) JS with liver involvement (COACH phenotype) and 12/76 (16%) MKS fetuses. No mutations were found in other JSRD subtypes, confirming the strong association between TMEM67 mutations and liver involvement. Literature review of all published TMEM67 mutated cases was performed to delineate genotype-phenotype correlates. In particular, comparison of the types of mutations and their distribution along the gene in lethal versus non lethal phenotypes showed in MKS patients a significant enrichment of missense mutations falling in TMEM67 exons 8 to 15, especially when in combination with a truncating mutation. These exons encode for a region of unknown function in the extracellular domain of meckelin. PMID:20232449

Untangling ciliary access and enrichment of two rhodopsin-like receptors using quantitative fluorescence microscopy reveals cell-specific sorting pathways.

PubMed

Geneva, Ivayla I; Tan, Han Yen; Calvert, Peter D

2017-02-15

Resolution limitations of optical systems are major obstacles for determining whether proteins are enriched within cell compartments. Here we use an approach to determine the degree of membrane protein ciliary enrichment that quantitatively accounts for the differences in sampling of the ciliary and apical membranes inherent to confocal microscopes. Theory shows that cilia will appear more than threefold brighter than the surrounding apical membrane when the densities of fluorescently labeled proteins are the same, thus providing a benchmark for ciliary enrichment. Using this benchmark, we examined the ciliary enrichment signals of two G protein-coupled receptors (GPCRs)-the somatostatin receptor 3 and rhodopsin. Remarkably, we found that the C-terminal VxPx motif, required for efficient enrichment of rhodopsin within rod photoreceptor sensory cilia, inhibited enrichment of the somatostatin receptor in primary cilia. Similarly, VxPx inhibited primary cilium enrichment of a chimera of rhodopsin and somatostatin receptor 3, where the dual Ax(S/A)xQ ciliary targeting motifs within the third intracellular loop of the somatostatin receptor replaced the third intracellular loop of rhodopsin. Rhodopsin was depleted from primary cilia but gained access, without being enriched, with the dual Ax(S/A)xQ motifs. Ciliary enrichment of these GPCRs thus operates via distinct mechanisms in different cells. © 2017 Geneva et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Reduced primary cilia length and altered Arl13b expression are associated with deregulated chondrocyte Hedgehog signaling in alkaptonuria.

PubMed

Thorpe, Stephen D; Gambassi, Silvia; Thompson, Clare L; Chandrakumar, Charmilie; Santucci, Annalisa; Knight, Martin M

2017-09-01

Alkaptonuria (AKU) is a rare inherited disease resulting from a deficiency of the enzyme homogentisate 1,2-dioxygenase which leads to the accumulation of homogentisic acid (HGA). AKU is characterized by severe cartilage degeneration, similar to that observed in osteoarthritis. Previous studies suggest that AKU is associated with alterations in cytoskeletal organization which could modulate primary cilia structure/function. This study investigated whether AKU is associated with changes in chondrocyte primary cilia and associated Hedgehog signaling which mediates cartilage degradation in osteoarthritis. Human articular chondrocytes were obtained from healthy and AKU donors. Additionally, healthy chondrocytes were treated with HGA to replicate AKU pathology (+HGA). Diseased cells exhibited shorter cilia with length reductions of 36% and 16% in AKU and +HGA chondrocytes respectively, when compared to healthy controls. Both AKU and +HGA chondrocytes demonstrated disruption of the usual cilia length regulation by actin contractility. Furthermore, the proportion of cilia with axoneme breaks and bulbous tips was increased in AKU chondrocytes consistent with defective regulation of ciliary trafficking. Distribution of the Hedgehog-related protein Arl13b along the ciliary axoneme was altered such that its localization was increased at the distal tip in AKU and +HGA chondrocytes. These changes in cilia structure/trafficking in AKU and +HGA chondrocytes were associated with a complete inability to activate Hedgehog signaling in response to exogenous ligand. Thus, we suggest that altered responsiveness to Hedgehog, as a consequence of cilia dysfunction, may be a contributing factor in the development of arthropathy highlighting the cilium as a novel target in AKU. © 2017 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals Inc.

Innovative approach to patient-centered care coordination in primary care practices.

PubMed

Clarke, Robin; Bharmal, Nazleen; Di Capua, Paul; Tseng, Chi-Hong; Mangione, Carol M; Mittman, Brian; Skootsky, Samuel A

2015-09-01

Although care coordination is an essential component of the patient-centered medical home structure, current case manager models have limited usefulness to population health because they typically serve a small group of patients defined based on disease or utilization. Our objective was to support our health system's population health by implementing and evaluating a program that embedded nonlicensed coordinators within our primary care practices to support physicians in executing care plans and communicating with patients. Matched case-control differences-in-differences. Comprehensive care coordinators (CCC) were introduced into 14 of the system's 28 practice sites in 2 waves. After a structured training program, CCCs identified, engaged, and intervened among patients within the practice in conjunction with practice primary care providers. We counted and broadly coded CCC activities that were documented in the intervention database. We examined the impact of CCC intervention on emergency department (ED) utilization at the practice level using a negative binomial multivariate regression model controlling for age, gender, and medical complexity. CCCs touched 10,500 unique patients over a 1-year period. CCC interventions included execution of care (38%), coordination of transitions (32%), self-management support/link to community resources (15%), monitor and follow-up (10%), and patient assessment (1%). The CCC intervention group had a 20% greater reduction in its prepost ED visit rate compared with the control group (P < .0001). Our CCC intervention demonstrated a significant reduction in ED visits by focusing on the centrality of the primary care provider and practice. Our model may serve as a cost-effective and scalable alternative for care coordination in primary care.

Continuous Coordination Tools and their Evaluation

NASA Astrophysics Data System (ADS)

Sarma, Anita; Al-Ani, Ban; Trainer, Erik; Silva Filho, Roberto S.; da Silva, Isabella A.; Redmiles, David; van der Hoek, André

This chapter discusses a set of co-ordination tools (the Continuous Co-ordination (CC) tool suite that includes Ariadne, Workspace Activity Viewer (WAV), Lighthouse, Palantír, and YANCEES) and details of our evaluation framework for these tools. Specifically, we discuss how we assessed the usefulness and the usability of these tools within the context of a predefined evaluation framework called DESMETDESMET . For example, for visualization tools we evaluated the suitability of the level of abstraction and the mode of displaying information of each tool. Whereas for an infrastructure tool we evaluate the effort required to implement co-ordination tools based on the given tool. We conclude with pointers on factors to consider when evaluating co-ordination tools in general.

Integrated primary care in Germany: the road ahead.

PubMed

Schlette, Sophia; Lisac, Melanie; Blum, Kerstin

2009-04-20

Health care delivery in Germany is highly fragmented, resulting in poor vertical and horizontal integration and a system that is focused on curing acute illness or single diseases instead of managing patients with more complex or chronic conditions, or managing the health of determined populations. While it is now widely accepted that a strong primary care system can help improve coordination and responsiveness in health care, primary care has so far not played this role in the German system. Primary care physicians traditionally do not have a gatekeeper function; patients can freely choose and directly access both primary and secondary care providers, making coordination and cooperation within and across sectors difficult. Since 2000, driven by the political leadership and initiative of the Federal Ministry of Health, the German Bundestag has passed several laws enabling new forms of care aimed to improve care coordination and to strengthen primary care as a key function in the German health care system. These include on the contractual side integrated care contracts, and on the delivery side disease management programmes, medical care centres, gatekeeping and 'community medicine nurses'. Recent policy reforms improved framework conditions for new forms of care. There is a clear commitment by the government and the introduction of selective contracting and financial incentives for stronger cooperation constitute major drivers for change. First evaluations, especially of disease management programmes, indicate that the new forms of care improve coordination and outcomes. Yet the process of strengthening primary care as a lever for better care coordination has only just begun. Future reforms need to address other structural barriers for change such as fragmented funding streams, inadequate payment systems, the lack of standardized IT systems and trans-sectoral education and training of providers.

Integrated primary care in Germany: the road ahead

PubMed Central

Schlette, Sophia; Lisac, Melanie; Blum, Kerstin

2009-01-01

Problem statement Health care delivery in Germany is highly fragmented, resulting in poor vertical and horizontal integration and a system that is focused on curing acute illness or single diseases instead of managing patients with more complex or chronic conditions, or managing the health of determined populations. While it is now widely accepted that a strong primary care system can help improve coordination and responsiveness in health care, primary care has so far not played this role in the German system. Primary care physicians traditionally do not have a gatekeeper function; patients can freely choose and directly access both primary and secondary care providers, making coordination and cooperation within and across sectors difficult. Description of policy development Since 2000, driven by the political leadership and initiative of the Federal Ministry of Health, the German Bundestag has passed several laws enabling new forms of care aimed to improve care coordination and to strengthen primary care as a key function in the German health care system. These include on the contractual side integrated care contracts, and on the delivery side disease management programmes, medical care centres, gatekeeping and ‘community medicine nurses’. Conclusion and discussion Recent policy reforms improved framework conditions for new forms of care. There is a clear commitment by the government and the introduction of selective contracting and financial incentives for stronger cooperation constitute major drivers for change. First evaluations, especially of disease management programmes, indicate that the new forms of care improve coordination and outcomes. Yet the process of strengthening primary care as a lever for better care coordination has only just begun. Future reforms need to address other structural barriers for change such as fragmented funding streams, inadequate payment systems, the lack of standardized IT systems and trans-sectoral education and training of providers. PMID:19513180

The role of Primary Healthcare in the coordination of Health Care Networks in Rio de Janeiro, Brazil, and Lisbon region, Portugal.

PubMed

Lapão, Luís Velez; Arcêncio, Ricardo Alexandre; Popolin, Marcela Paschoal; Rodrigues, Ludmila Barbosa Bandeira

2017-03-01

Considering the trajectory of Rio de Janeiro e Lisboa region regarding strengths of the their health local systems to achieve health for all and equity, the study aimed to compare the organization of the Primary Healthcare from both regions, searching to identify the advancement which in terms of the Delivery Health Networks' coordination. It is a case study with qualitative approach and assessment dimensions. It was used material available online such as scientific manuscripts and gray literature. The results showed the different grades regarding Delivery Health Networks. Lisboa region present more advancement, because of its historic issues, it has implemented Primary Healthcare expanded and nowadays it achieved enough maturity related to coordination of its health local system and Rio de Janeiro suffers still influence from historic past regarding Primary Healthcare selective. The both regions has done strong bids in terms of electronic health records and telemedicine. After of the study, it is clearer the historic, cultural and politics and legal issue that determined the differences of the Primary Healthcare coordinator of the Delivery Health Network in Rio de Janeiro and Lisboa region.

Regional variation in interhemispheric coordination of intrinsic hemodynamic fluctuations.

PubMed

Stark, David E; Margulies, Daniel S; Shehzad, Zarrar E; Reiss, Philip; Kelly, A M Clare; Uddin, Lucina Q; Gee, Dylan G; Roy, Amy K; Banich, Marie T; Castellanos, F Xavier; Milham, Michael P

2008-12-17

Electrophysiological studies have long demonstrated a high degree of correlated activity between the left and right hemispheres, however little is known about regional variation in this interhemispheric coordination. Whereas cognitive models and neuroanatomical evidence suggest differences in coordination across primary sensory-motor cortices versus higher-order association areas, these have not been characterized. Here, we used resting-state functional magnetic resonance imaging data acquired from 62 healthy volunteers to examine interregional correlation in spontaneous low-frequency hemodynamic fluctuations. Using a probabilistic atlas, we correlated probability-weighted time series from 112 regions comprising the entire cerebrum. We then examined regional variation in correlated activity between homotopic regions, contrasting primary sensory-motor cortices, unimodal association areas, and heteromodal association areas. Consistent with previous studies, robustly correlated spontaneous activity was noted between all homotopic regions, which was significantly higher than that between nonhomotopic (heterotopic and intrahemispheric) regions. We further demonstrated substantial regional variation in homotopic interhemispheric correlations that was highly consistent across subjects. Specifically, there was a gradient of interhemispheric correlation, with highest correlations across primary sensory-motor cortices (0.758, SD=0.152), significantly lower correlations across unimodal association areas (0.597, SD=0.230) and still lower correlations across heteromodal association areas (0.517, SD=0.226). These results demonstrate functional differences in interhemispheric coordination related to the brain's hierarchical subdivisions. Synchrony across primary cortices may reflect networks engaged in bilateral sensory integration and motor coordination, whereas lower coordination across heteromodal association areas is consistent with functional lateralization of these regions. This novel method of examining interhemispheric coordination may yield insights regarding diverse disease processes as well as healthy development.

A new index for characterizing micro-bead motion in a flow induced by ciliary beating: Part II, modeling

PubMed Central

Bottier, Mathieu; Peña Fernández, Marta; Pelle, Gabriel; Grotberg, James B.

2017-01-01

Mucociliary clearance is one of the major lines of defense of the human respiratory system. The mucus layer coating the airways is constantly moved along and out of the lung by the activity of motile cilia, expelling at the same time particles trapped in it. The efficiency of the cilia motion can experimentally be assessed by measuring the velocity of micro-beads traveling through the fluid surrounding the cilia. Here we present a mathematical model of the fluid flow and of the micro-beads motion. The coordinated movement of the ciliated edge is represented as a continuous envelope imposing a periodic moving velocity boundary condition on the surrounding fluid. Vanishing velocity and vanishing shear stress boundary conditions are applied to the fluid at a finite distance above the ciliated edge. The flow field is expanded in powers of the amplitude of the individual cilium movement. It is found that the continuous component of the horizontal velocity at the ciliated edge generates a 2D fluid velocity field with a parabolic profile in the vertical direction, in agreement with the experimental measurements. Conversely, we show than this model can be used to extract microscopic properties of the cilia motion by extrapolating the micro-bead velocity measurement at the ciliated edge. Finally, we derive from these measurements a scalar index providing a direct assessment of the cilia beating efficiency. This index can easily be measured in patients without any modification of the current clinical procedures. PMID:28708866

Care coordination and provider stress in primary care management of high-risk patients.

PubMed

Okunogbe, Adeyemi; Meredith, Lisa S; Chang, Evelyn T; Simon, Alissa; Stockdale, Susan E; Rubenstein, Lisa V

2018-01-01

Care coordination is a critical component of managing high-risk patients, who tend to have complex and multiple medical and psychosocial problems and are typically at high risk for increased hospitalization and incur high health care expenditures. Primary care models such as the patient-centered medical homes (PCMHs) are designed to improve care coordination and reduce care fragmentation. However, little is known about how the burden of care coordination for high-risk patients influences PCMH team members' stress. To evaluate the relationship between provider stress and care coordination time in high-risk patient care and whether availability of help is associated with reduced stress. Multivariable regression analysis of a cross-sectional survey of PCMH primary care providers (PCPs) and nurses. A total of 164 PCPs and 272 nurses in primary care practices at five geographically diverse Veteran Health Administration (VA) medical center health systems. The main outcome variable was provider stress due to high-risk patient care. Independent variables were the reported proportion of high-risk patients in PCP/nurse patient panels, time spent coordinating care for these patients, and provider satisfaction with help received in caring for them. The response rate was 44%. Spending more than 8 h per week coordinating care was significantly associated with a 0.21-point increase in reported provider stress compared to spending 8 h or less per week (95% CI: 0.04-0.39; p = 0.015). The magnitude of the association between stress and care coordination time was diminished when provider satisfaction with help received was included in the model. Perceived provider stress from care of high-risk patients may arise from challenges related to coordinating their care. Our findings suggest that the perception of receiving help for high-risk patient care may be valuable in reducing provider stress.

Meaningful use care coordination criteria: Perceived barriers and benefits among primary care providers.

PubMed

Cohen, Genna R; Adler-Milstein, Julia

2016-04-01

Stage 2 and proposed Stage 3 meaningful use criteria ask providers to support patient care coordination by electronically generating, exchanging, and reconciling key information during patient care transitions. A stratified random sample of primary care practices in Michigan (n = 328) that had already met Stage 1 meaningful use criteria was surveyed, in order to identify the anticipated barriers to meeting these criteria as well as the expected impact on patient care coordination from doing so. The top three barriers, as identified by >65% of the primary care providers surveyed, were difficulty sending and receiving patient information electronically, a lack of provider and practice staff time, and the complex workflow changes required. Despite these barriers, primary care providers expressed strong agreement that meeting the proposed Stage 3 care coordination criteria would improve their patients' treatment and ensure they know about their patients' visits to other providers. The survey results suggest the need to enhance policy approaches and organizational strategies to address the key barriers identified by providers and practices in order to realize important care coordination benefits. © The Author 2015. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Multidisciplinary coordinated care for Type 2 diabetes: A qualitative analysis of patient perspectives.

PubMed

Berkowitz, Seth A; Eisenstat, Stephanie A; Barnard, Lily S; Wexler, Deborah J

2018-06-01

To explore the patient perspective on coordinated multidisciplinary diabetes team care among a socioeconomically diverse group of adults with type 2 diabetes. Qualitative research design using 8 focus groups (n=53). We randomly sampled primary care patients with type 2 diabetes and conducted focus groups at their primary care clinic. Discussion prompts queried current perceptions of team care. Each focus group was audio recorded, transcribed verbatim, and independently coded by three reviewers. Coding used an iterative process. Thematic saturation was achieved. Data were analyzed using content analysis. Most participants believed that coordinated multidisciplinary diabetes team care was a good approach, feeling that diabetes was too complicated for any one care team member to manage. Primary care physicians were seen as too busy to manage diabetes alone, and participants were content to be treated by other care team members, especially if there was a single point of contact and the care was coordinated. Participants suggested that an ideal multidisciplinary approach would additionally include support for exercise and managing socioeconomic challenges, components perceived to be missing from the existing approach to diabetes care. Coordinated, multidisciplinary diabetes team care is understood by and acceptable to patients with type 2 diabetes. Copyright © 2018 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

From ICT Coordination to ICT Integration: A Longitudinal Case Study

ERIC Educational Resources Information Center

Tondeur, J.; Cooper, M.; Newhouse, C. P.

2010-01-01

This study utilizes a school-improvement perspective to examine the role of curriculum coordination in the integration of information and communication technologies (ICT) into primary schools. The nature and impact of this role is examined in seven primary schools in Australia. These seven schools were drawn from a longitudinal intervention that…

Cognitive Motor Coordination Training Improves Mental Rotation Performance in Primary School-Aged Children

ERIC Educational Resources Information Center

Pietsch, Stefanie; Böttcher, Caroline; Jansen, Petra

2017-01-01

The long-term physical activity in specific sport activities can change the quality of mental rotation performance. This study investigates the influence of "Life Kinetik"--a motion program with tasks of cognition and motor coordination--on mental rotation performance of 44 primary school-aged children. While the experimental group…

Care pathways across the primary-hospital care continuum: using the multi-level framework in explaining care coordination

PubMed Central

2013-01-01

Background Care pathways are widely used in hospitals for a structured and detailed planning of the care process. There is a growing interest in extending care pathways into primary care to improve quality of care by increasing care coordination. Evidence is sparse about the relationship between care pathways and care coordination. The multi-level framework explores care coordination across organizations and states that (inter)organizational mechanisms have an effect on the relationships between healthcare professionals, resulting in quality and efficiency of care. The aim of this study was to assess the extent to which care pathways support or create elements of the multi-level framework necessary to improve care coordination across the primary - hospital care continuum. Methods This study is an in-depth analysis of five existing local community projects located in four different regions in Flanders (Belgium) to determine whether the available empirical evidence supported or refuted the theoretical expectations from the multi-level framework. Data were gathered using mixed methods, including structured face-to-face interviews, participant observations, documentation and a focus group. Multiple cases were analyzed performing a cross case synthesis to strengthen the results. Results The development of a care pathway across the primary-hospital care continuum, supported by a step-by-step scenario, led to the use of existing and newly constructed structures, data monitoring and the development of information tools. The construction and use of these inter-organizational mechanisms had a positive effect on exchanging information, formulating and sharing goals, defining and knowing each other’s roles, expectations and competences and building qualitative relationships. Conclusion Care pathways across the primary-hospital care continuum enhance the components of care coordination. PMID:23919518

Care pathways across the primary-hospital care continuum: using the multi-level framework in explaining care coordination.

PubMed

Van Houdt, Sabine; Heyrman, Jan; Vanhaecht, Kris; Sermeus, Walter; De Lepeleire, Jan

2013-08-06

Care pathways are widely used in hospitals for a structured and detailed planning of the care process. There is a growing interest in extending care pathways into primary care to improve quality of care by increasing care coordination. Evidence is sparse about the relationship between care pathways and care coordination.The multi-level framework explores care coordination across organizations and states that (inter)organizational mechanisms have an effect on the relationships between healthcare professionals, resulting in quality and efficiency of care.The aim of this study was to assess the extent to which care pathways support or create elements of the multi-level framework necessary to improve care coordination across the primary-hospital care continuum. This study is an in-depth analysis of five existing local community projects located in four different regions in Flanders (Belgium) to determine whether the available empirical evidence supported or refuted the theoretical expectations from the multi-level framework. Data were gathered using mixed methods, including structured face-to-face interviews, participant observations, documentation and a focus group. Multiple cases were analyzed performing a cross case synthesis to strengthen the results. The development of a care pathway across the primary-hospital care continuum, supported by a step-by-step scenario, led to the use of existing and newly constructed structures, data monitoring and the development of information tools. The construction and use of these inter-organizational mechanisms had a positive effect on exchanging information, formulating and sharing goals, defining and knowing each other's roles, expectations and competences and building qualitative relationships. Care pathways across the primary-hospital care continuum enhance the components of care coordination.

Lower fragmentation of coordination in primary care is associated with lower prescribing drug costs-lessons from chronic illness care in Hungary.

PubMed

Lublóy, Ágnes; Keresztúri, Judit Lilla; Benedek, Gábor

2017-10-01

Improving patient care coordination is critical for achieving better health outcome measures at reduced cost. However, assessing the results of patient care coordination at system level is lacking. In this report, based on administrative healthcare data, a provider-level care coordination measure is developed to assess the function of primary care at system level. In a sample of 31 070 patients with diabetes we find that the type of collaborative relationship general practitioners build up with specialists is associated with prescription drug costs. Regulating access to secondary care might result in cost savings through improved care coordination. © The Author 2017. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

Implementation of an integrated primary care cardiometabolic risk prevention and management network in Montréal: does greater coordination of care with primary care physicians have an impact on health outcomes?

PubMed

Provost, Sylvie; Pineault, Raynald; Grimard, Dominique; Pérez, José; Fournier, Michel; Lévesque, Yves; Desforges, Johanne; Tousignant, Pierre; Borgès Da Silva, Roxane

2017-04-01

Chronic disease management requires substantial services integration. A cardiometabolic risk management program inspired by the Chronic Care Model was implemented in Montréal for patients with diabetes or hypertension. One of this study's objectives was to assess the impact of care coordination between the interdisciplinary teams and physicians on patient participation in the program, lifestyle improvements and disease control. We obtained data on health outcomes from a register of clinical data, questionnaires completed by patients upon entry into the program and at the 12-month mark, and we drew information on the program's characteristics from the implementation analysis. We conducted multiple regression analyses, controlling for patient sociodemographic and health characteristics, to measure the association between interdisciplinary team coordination with primary care physicians and various health outcomes. A total of 1689 patients took part in the study (60.1% participation rate). Approximately 40% of patients withdrew from the program during the first year. At the 12-month follow-up (n = 992), we observed a significant increase in the proportion of patients achieving the various clinical targets. The perception by the interdisciplinary team of greater care coordination with primary care physicians was associated with increased participation in the program and the achievement of better clinical results. Greater coordination of patient services between interdisciplinary teams and primary care physicians translates into benefits for patients.

After-hours care and its coordination with primary care in the U.S.

PubMed

O'Malley, Ann S; Samuel, Divya; Bond, Amelia M; Carrier, Emily

2012-11-01

Despite expectations that medical homes provide "24 × 7 coverage" there is little to guide primary care practices in developing sustainable models for accessible and coordinated after-hours care. To identify and describe models of after-hours care in the U.S. that are delivered in primary care sites or coordinated with a patient's usual primary care provider. Qualitative analysis of data from in-depth telephone interviews. Primary care practices in 16 states and the organizations they partner with to provide after-hours coverage. Forty-four primary care physicians, practice managers, nurses and health plan representatives from 28 organizations. Analyses examined after-hours care models, facilitators, barriers and lessons learned. Based on 28 organizations interviewed, five broad models of after-hours care were identified, ranging in the extent to which they provide continuity and patient access. Key themes included: 1) The feasibility of a model varies for many reasons, including patient preferences and needs, the local health care market supply, and financial compensation; 2) A shared electronic health record and systematic notification procedures were extremely helpful in maintaining information continuity between providers; and 3) after-hours care is best implemented as part of a larger practice approach to access and continuity. After-hours care coordinated with a patient's usual primary care provider is facilitated by consideration of patient demand, provider capacity, a shared electronic health record, systematic notification procedures and a broader practice approach to improving primary care access and continuity. Payer support is important to increasing patients' access to after-hours care.

The effect of implementing a care coordination program on team dynamics and the patient experience.

PubMed

Di Capua, Paul; Clarke, Robin; Tseng, Chi-Hong; Wilhalme, Holly; Sednew, Renee; McDonald, Kathryn M; Skootsky, Samuel A; Wenger, Neil

2017-08-01

Care coordination programs are frequently implemented in the redesign of primary care systems, focused on improving patient outcomes and reducing utilization. However, redesign can be disruptive, affect patient experiences, and undermine elements in the patient-centered medical home, such as team-based care. Case-controlled study with difference-in-differences (DID) and cross-sectional analyses. The phased implementation of a care coordination program permitted evaluation of a natural experiment to compare measures of patient experience and teamwork in practices with and without care coordinators. Patient experience scores were compared before and after the introduction of care coordinators, using DID analyses. Cross-sectional data were used to compare teamwork, based on the relational coordination survey, and physician-perceived barriers to coordinated care between clinics with and without care coordinators. We evaluated survey responses from 459 staff and physicians and 13,441 patients in 26 primary care practices. Practices with care coordinators did not have significantly different relational coordination scores compared with practices without care coordinators, and physicians in these practices did not report reduced barriers to coordinated care. After implementation of the program, patients in practices with care coordinators reported a more positive experience with staff over time (DID, 2.6 percentage points; P = .0009). A flexible program that incorporates care coordinators into the existing care team was minimally disruptive to existing team dynamics, and the embedded care coordinators were associated with a small increase in patient ratings that reflected a more positive experience with staff.

Doctors' opinion on the contribution of coordination mechanisms to improving clinical coordination between primary and outpatient secondary care in the Catalan national health system.

PubMed

Aller, Marta-Beatriz; Vargas, Ingrid; Coderch, Jordi; Vázquez, Maria-Luisa

2017-12-22

Clinical coordination is considered a health policy priority as its absence can lead to poor quality of care and inefficiency. A key challenge is to identify which strategies should be implemented to improve coordination. The aim is to analyse doctors' opinions on the contribution of mechanisms to improving clinical coordination between primary and outpatient secondary care and the factors influencing their use. A qualitative descriptive study in three healthcare networks of the Catalan national health system. A two-stage theoretical sample was designed: in the first stage, networks with different management models were selected; in the second, primary care (n = 26) and secondary care (n = 24) doctors. Data were collected using semi-structured interviews. Final sample size was reached by saturation. A thematic content analysis was conducted, segmented by network and care level. With few differences across networks, doctors identified similar mechanisms contributing to clinical coordination: 1) shared EMR facilitating clinical information transfer and uptake; 2) mechanisms enabling problem-solving communication and agreement on clinical approaches, which varied across networks (joint clinical case conferences, which also promote mutual knowledge and training of primary care doctors; virtual consultations through EMR and email); and 3) referral protocols and use of the telephone facilitating access to secondary care after referrals. Doctors identified organizational (insufficient time, incompatible timetables, design of mechanisms) and professional factors (knowing each other, attitude towards collaboration, concerns over misdiagnosis) that influence the use of mechanisms. Mechanisms that most contribute to clinical coordination are feedback mechanisms, that is those based on mutual adjustment, that allow doctors to exchange information and communicate. Their use might be enhanced by focusing on adequate working conditions, mechanism design and creating conditions that promote mutual knowledge and positive attitudes towards collaboration.

Loss of Centrobin Enables Daughter Centrioles to Form Sensory Cilia in Drosophila.

PubMed

Gottardo, Marco; Pollarolo, Giulia; Llamazares, Salud; Reina, Jose; Riparbelli, Maria G; Callaini, Giuliano; Gonzalez, Cayetano

2015-08-31

Sensory cilia are organelles that convey information to the cell from the extracellular environment. In vertebrates, ciliary dysfunction results in ciliopathies that in humans comprise a wide spectrum of developmental disorders. In Drosophila, sensory cilia are found only in the neurons of type I sensory organs, but ciliary dysfunction also has dramatic consequences in this organism because it impairs the mechanosensory properties of bristles and chaetae and leads to uncoordination, a crippling condition that causes lethality shortly after eclosion. The cilium is defined by the ciliary membrane, a protrusion of the cell membrane that envelops the core structure known as the axoneme, a microtubule array that extends along the cilium from the basal body. In vertebrates, basal body function requires centriolar distal and subdistal appendages and satellites. Because these structures are acquired through centriole maturation, only mother centrioles can serve as basal bodies. Here, we show that although centriole maturity traits are lacking in Drosophila, basal body fate is reserved to mother centrioles in Drosophila type I neurons. Moreover, we show that depletion of the daughter-centriole-specific protein Centrobin (CNB) enables daughter centrioles to dock on the cell membrane and to template an ectopic axoneme that, although structurally defective, protrudes out of the cell and is enveloped by a ciliary membrane. Conversely, basal body capability is inhibited in mother centrioles modified to carry CNB. These results reveal the crucial role of CNB in regulating basal body function in Drosophila ciliated sensory organs. Copyright © 2015 Elsevier Ltd. All rights reserved.

Mechanics of membrane-cytoskeleton attachment in Paramecium

NASA Astrophysics Data System (ADS)

Campillo, C.; Jerber, J.; Fisch, C.; Simoes-Betbeder, M.; Dupuis-Williams, P.; Nassoy, P.; Sykes, C.

2012-12-01

In this paper we assess the role of the protein MKS1 (Meckel syndrome type 1) in the cortical membrane mechanics of the ciliated protist Paramecium. This protein is known to be crucial in the process of cilium formation, and we investigate its putative role in membrane-cytoskeleton attachment. Therefore, we compare cells where the gene coding for MKS1 is silenced to wild-type cells. We found that scanning electron microscopy observation of the cell surface reveals a cup-like structure in wild-type cells that is lost in silenced cells. Since this structure is based on the underlying cytoskeleton, one hypothesis to explain this observation is a disruption of membrane attachment to the cytoskeleton in the absence of MKS1 that should affect plasma membrane mechanics. We test this by probing the mechanics of wild-type and silenced cells by micropipette aspiration. Strikingly, we observe that, at the same aspiration pressure, the membrane of silenced cells is easily aspirated by the micropipette whereas that of wild-type cells enters only at a moderate velocity, an effect that suggests a detachment of the membrane from the underlying cytoskeleton in silenced cells. We quantify this detachment by measuring the deformation of the cell cortex and the rate of cell membrane entry in the micropipette. This study offers a new perspective for the characterization of membrane-cytoskeleton attachment in protists and paves the way for a better understanding of the role of membrane-cortex attachment in cilium formation.

[Better coordination between primary care, community settings and diabetes outpatient clinic for patients with type 2 diabetes].

PubMed

Gjessing, Hans Jørgen; Jørgensen, Ulla Linding; Møller, Charlotte Chrois; Huge, Lis; Dalgaard, Anne Mette; Nielsen, Kristian Wendelboe; Thomsen, Lis; Buch, Martin Sandberg

2014-06-02

Integrated care programmes for patients with type 2 diabetes can be successfully implemented by planning the programmes in coordination between the sectors primary care, community settings and diabetes outpatient clinic, and with involvement of leaders and employees. Our project has resulted in: 1) more patients with type 2 diabetes receiving diabetes management courses, 2) improved diabetes management of primary care, and 3) improved confidence and respect between sectors involved in diabetes care.

Practical applications of the geographic coordinate data base in Arkansas

Treesearch

Mickie Warwick; Don C. Bragg

2005-01-01

Though not intended for these applications, the General Land Office (GLO) survey notes are a primary source of historical, ecological, and cultural information, making it imperative that their spatial coordinates be as reliable as possible. The Geographic Coordinate Data Base (GCDB) is a statistically-based coordinate fitting program that uses the GLO notes and other...

Study protocol: identifying and delivering point-of-care information to improve care coordination.

PubMed

Hysong, Sylvia J; Che, Xinxuan; Weaver, Sallie J; Petersen, Laura A

2015-10-19

The need for deliberately coordinated care is noted by many national-level organizations. The Department of Veterans Affairs (VA) recently transitioned primary care clinics nationwide into Patient Aligned Care Teams (PACTs) to provide more accessible, coordinated, comprehensive, and patient-centered care. To better serve this purpose, PACTs must be able to successfully sequence and route interdependent tasks to appropriate team members while also maintaining collective situational awareness (coordination). Although conceptual frameworks of care coordination exist, few explicitly articulate core behavioral markers of coordination or the related information needs of team members attempting to synchronize complex care processes across time for a shared patient population. Given this gap, we partnered with a group of frontline primary care personnel at ambulatory care sites to identify the specific information needs of PACT members that will enable them to coordinate their efforts to provide effective, coordinated care. The study has three objectives: (1) development of measurable, prioritized point-of-care criteria for effective PACT coordination; (2) identifying the specific information needed at the point of care to optimize coordination; and (3) assessing the effect of adopting the aforementioned coordination standards on PACT clinicians' coordination behaviors. The study consists of three phases. In phase 1, we will employ the Productivity Measurement and Enhancement System (ProMES), a structured approach to performance measure creation from industrial/organizational psychology, to develop coordination measures with a design team of 6-10 primary care personnel; in phase 2, we will conduct focus groups with the phase 1 design team to identify point-of-care information needs. Phase 3 is a two-arm field experiment (n PACT = 28/arm); intervention arm PACTs will receive monthly feedback reports using the measures developed in phase 1 and attend brief monthly feedback sessions. Control arm PACTs will receive no intervention. PACTs will be followed prospectively for up to 1 year. This project combines both action research and implementation science methods to address important gaps in the existing care coordination literature using a partnership-based research design. It will provide an evidence-based framework for care coordination by employing a structured methodology for a systematic approach to care coordination in PACT settings and identifying the information needs that produce the most successful coordination of care. ISRCTN15412521.

[Use of social and health primary care services for older people with complex needs: Comparison of three types of gerontological coordination].

PubMed

de Stampa, M; Bagaragaza, E; Herr, M; Aegerter, P; Vedel, I; Bergman, H; Ankri, J

2014-10-01

Older people with complex needs live mainly at home. Several types of gerontological coordinations have been established on the French territory to meet their needs and to implement social and primary health care services. But we do not have any information on the use of these services at home as a function of the coordination method used. We compared the use of home care services for older people with complex needs in three types of coordination with 12 months' follow-up. The three coordinations regrouped a gerontological network with case management (n=105 persons), a nursing home service (SSIAD) with a nurse coordination (n=206 persons) and an informal coordination with a non-professional caregiver (n=117 persons). At t0, the older people addressed to the gerontological network had less access to the services offered at home; those followed by the SSIAD had the highest number of services and of weekly interventions. Hours of weekly services were two-fold higher in those with the informal coordination. At t12, there was an improvement in access to services for the network group with case management and an overall increase in the use of professional services at home with no significant difference between the three groups. The use of social and primary health care services showed differences between the three gerontological coordinations. The one-year evolution in the use of home services was comparable between the groups without an explosion in the number of services in the network group with case management. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Primary care nursing role and care coordination: an observational study of nursing work in a community health center.

PubMed

Anderson, Daren R; St Hilaire, Daniel; Flinter, Margaret

2012-05-31

Care coordination is a core element of the Patient-Centered Medical Home and requires an effective, well educated nursing staff. A greater understanding of roles and tasks currently being carried out by nurses in primary care is needed to help practices determine how best to implement care coordination and transform into PCMHs. We conducted an observational study of primary care nursing in a Community Health Center by creating a classification schema for nursing responsibilities, directly observing and tracking nurses' work, and categorizing their activities. Ten nurses in eight different practice sites were observed for a total of 61 hours. The vast majority of nursing time was spent in vaccine and medication administration; telephone work; and charting and paper work, while only 15% of their time was spent in activity that was classified broadly as care coordination. Care coordination work appeared to be subsumed by other daily tasks, many of which could have been accomplished by other, lesser trained members of the health care team. Practices looking to implement care coordination need a detailed look at work flow, task assignments, and a critical assessment of staffing, adhering to the principal of each team member working to the highest level of his or her education and license. Care coordination represents a distinct responsibility that requires dedicated nursing time, separate from the day to day tasks in a busy practice. To fully support these new functions, reimbursement models are needed that support such non visit-based work and provide incentives to coordinate and manage complex cases, achieve improved clinical outcomes and enhance efficiency of the health system. This article describes our study methods, data collection, and analysis, results, and discussion about reorganizing nursing roles to promote care coordination.

Impact of health literacy, accessibility and coordination of care on patient's satisfaction with primary care in Germany.

PubMed

Altin, Sibel Vildan; Stock, Stephanie

2015-10-22

Although health policy makers call for the transformation of health care organizations to health literacy responsive ones, there is limited evidence on the care experiences of patients with limited health literacy skills (HL) in respect to health care quality. We explored if HL and patient-reported experiences regarding access to care and support in care-coordination in primary care organizations (PCO) have an impact on patients satisfaction with the care received by their personal general practitioner (GP). A nationwide representative survey was administered in a random sample of 1125 German adults. Binary logistic regression analyses were performed to determine whether HL and perceived access to and coordination of care were associated with satisfaction with care received in primary care adjusting for demographics and health status. In the unadjusted as well as adjusted model, better accessibility of the primary care practice (β= 1.858; 2.032 p < 0.001) frequent support in care coordination by the general practitioner (β = 2.680; 2.820 p < 0.001) as well as sufficient HL (β = 0.888; 1.228 p < 0.05) were independent predictors of a higher satisfaction with care received in the general practice. German adults with sufficient HL and positive experiences regarding care coordination and access to care are more satisfied with care received by their personal general practitioner. This result is from major importance for primary care organizations intending to transform their processes and structures to respond to the health literacy needs of their patients more effectively.

The next step towards making use meaningful: electronic information exchange and care coordination across clinicians and delivery sites.

PubMed

Graetz, Ilana; Reed, Mary; Shortell, Stephen M; Rundall, Thomas G; Bellows, Jim; Hsu, John

2014-12-01

Care for patients with chronic conditions often requires coordination between multiple physicians and delivery sites. Electronic Health Record (EHR) use could improve care quality and efficiency in part by facilitating care coordination. We examined the association between EHR use and clinician perceptions of care coordination for patients transferred across clinicians and delivery sites. Repeated surveys of primary care clinicians during the staggered implementation of an outpatient EHR (2005-2008), followed by an integrated inpatient EHR (2006-2010). We measured the association between EHR use stages (no use, outpatient EHR only, and integrated inpatient-outpatient EHR) and care coordination using logistic regression, adjusting for clinician characteristics, study year, and medical center. Adult primary care clinicians in a large Integrated Delivery System. Three measures of clinician-reported care coordination for patient care transferred across clinicians (eg, from specialist to primary care team) and across delivery sites (eg, from the hospital to outpatient care). Outpatient EHR use was associated with higher reports of access to complete and timely clinical information and higher agreement on clinician roles and responsibilities for patients transferred across clinicians, but not for patients transferred across delivery sites. Use of the integrated outpatient-inpatient EHR was associated with higher reports of access to timely and complete clinical information, clinician agreement on the patient's treatment plan for patients transferred across delivery sites, and with all coordination measures for patients transferred across clinicians. Use of an integrated EHR with health information exchange across delivery settings improved patient care coordination.

Improving EHR Capabilities to Facilitate Stage 3 Meaningful Use Care Coordination Criteria.

PubMed

Cross, Dori A; Cohen, Genna R; Nong, Paige; Day, Anya-Victoria; Vibbert, Danielle; Naraharisetti, Ramya; Adler-Milstein, Julia

Primary care practices have been limited in their ability to leverage electronic health records (EHRs) and health information exchange (HIE) to improve care coordination, but will soon be incentivized to do so under proposed Stage 3 meaningful use criteria. We use mixed methods to understand how primary care practices manage, share and reconcile electronic patient information across care settings, and identify innovations in EHR design to support enhanced care coordination. Opportunities identified by practices focused on availability and usability of features that facilitate (1) generation of customized summary of care records, (2) team-based care approaches, and (3) management of the increased volume of electronic information generated and exchanged during care transitions. More broadly, vendors and policymakers need to continue to work together to improve interoperability as the key to effective care coordination. If these EHR innovations were widespread, the value of meeting the proposed Stage 3 care coordination criteria would be substantially enhanced.

[Healthcare promotion in primary care: if Hippocrates were alive today…].

PubMed

Cabeza, Elena; March, Sebastià; Cabezas, Carmen; Segura, Andreu

2016-11-01

This article argues for the need to implement community healthcare promotion initiatives in medical practice. Some of the community initiatives introduced in primary care, as well as scientific evidence and associated implementation factors are described. The need for effective coordination between primary care and public health services, working with the community, is underlined. Two specific coordination initiatives are explained by way of example. The first is a project to develop healthcare plans in health centres in the Balearic Islands, by means of a participatory process with the collaboration of citizens, local organisations and the town council (urban planning, mobility, social services, etc.). The second is the Interdepartmental Public Health Plan of Catalonia, which was established to coordinate cross-sectoral healthcare. A specific part of this plan is the COMSalud project, the purpose of which is to introduce a community perspective to health centres and which is currently being piloted in 16 health areas. We review the proposals of a 2008 research study to implement healthcare promotion in primary care, assessing its achievements and shortfalls. The Disease Prevention and Health Promotion Strategy of the Spanish Ministry of Health is recognised as an opportunity to coordinate primary and public health. It is concluded that this change of mentality will require both financial and human resources to come to fruition. Copyright © 2016 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

Primary Health Care: care coordinator in regionalized networks?

PubMed Central

de Almeida, Patty Fidelis; dos Santos, Adriano Maia

2016-01-01

RESUMO OBJECTIVE To analyze the breadth of care coordination by Primary Health Care in three health regions. METHODS This is a quantitative and qualitative case study. Thirty-one semi-structured interviews with municipal, regional and state managers were carried out, besides a cross-sectional survey with the administration of questionnaires to physicians (74), nurses (127), and a representative sample of users (1,590) of Estratégia Saúde da Família (Family Health Strategy) in three municipal centers of health regions in the state of Bahia. RESULTS Primary Health Care as first contact of preference faced strong competition from hospital outpatient and emergency services outside the network. Issues related to access to and provision of specialized care were aggravated by dependence on the private sector in the regions, despite progress observed in institutionalizing flows starting out from Primary Health Care. The counter-referral system was deficient and interprofessional communication was scarce, especially concerning services provided by the contracted network. CONCLUSIONS Coordination capacity is affected both by the fragmentation of the regional network and intrinsic problems in Primary Health Care, which poorly supported in its essential attributes. Although the health regions have common problems, Primary Health Care remains a subject confined to municipal boundaries. PMID:28099663

Phenotypic spectrum and prevalence of INPP5E mutations in Joubert syndrome and related disorders.

PubMed

Travaglini, Lorena; Brancati, Francesco; Silhavy, Jennifer; Iannicelli, Miriam; Nickerson, Elizabeth; Elkhartoufi, Nadia; Scott, Eric; Spencer, Emily; Gabriel, Stacey; Thomas, Sophie; Ben-Zeev, Bruria; Bertini, Enrico; Boltshauser, Eugen; Chaouch, Malika; Cilio, Maria Roberta; de Jong, Mirjam M; Kayserili, Hulya; Ogur, Gonul; Poretti, Andrea; Signorini, Sabrina; Uziel, Graziella; Zaki, Maha S; Johnson, Colin; Attié-Bitach, Tania; Gleeson, Joseph G; Valente, Enza Maria

2013-10-01

Joubert syndrome and related disorders (JSRD) are clinically and genetically heterogeneous ciliopathies sharing a peculiar midbrain-hindbrain malformation known as the 'molar tooth sign'. To date, 19 causative genes have been identified, all coding for proteins of the primary cilium. There is clinical and genetic overlap with other ciliopathies, in particular with Meckel syndrome (MKS), that is allelic to JSRD at nine distinct loci. We previously identified the INPP5E gene as causative of JSRD in seven families linked to the JBTS1 locus, yet the phenotypic spectrum and prevalence of INPP5E mutations in JSRD and MKS remain largely unknown. To address this issue, we performed INPP5E mutation analysis in 483 probands, including 408 JSRD patients representative of all clinical subgroups and 75 MKS fetuses. We identified 12 different mutations in 17 probands from 11 JSRD families, with an overall 2.7% mutation frequency among JSRD. The most common clinical presentation among mutated families (7/11, 64%) was Joubert syndrome with ocular involvement (either progressive retinopathy and/or colobomas), while the remaining cases had pure JS. Kidney, liver and skeletal involvement were not observed. None of the MKS fetuses carried INPP5E mutations, indicating that the two ciliopathies are not allelic at this locus.

Basal cell carcinoma pathogenesis and therapy involving hedgehog signaling and beyond.

PubMed

Bakshi, Anshika; Chaudhary, Sandeep C; Rana, Mehtab; Elmets, Craig A; Athar, Mohammad

2017-12-01

Basal cell carcinoma (BCC) of the skin is driven by aberrant hedgehog signaling. Thus blocking this signaling pathway by small molecules such as vismodegib inhibits tumor growth. Primary cilium in the epidermal cells plays an integral role in the processing of hedgehog signaling-related proteins. Recent genomic studies point to the involvement of additional genetic mutations that might be associated with the development of BCCs, suggesting significance of other signaling pathways, such as WNT, NOTCH, mTOR, and Hippo, aside from hedgehog in the pathogenesis of this human neoplasm. Some of these pathways could be regulated by noncoding microRNA. Altered microRNA expression profile is recognized with the progression of these lesions. Stopping treatment with Smoothened (SMO) inhibitors often leads to tumor reoccurrence in the patients with basal cell nevus syndrome, who develop 10-100 of BCCs. In addition, the initial effectiveness of these SMO inhibitors is impaired due to the onset of mutations in the drug-binding domain of SMO. These data point to a need to develop strategies to overcome tumor recurrence and resistance and to enhance efficacy by developing novel single agent-based or multiple agents-based combinatorial approaches. Immunotherapy and photodynamic therapy could be additional successful approaches particularly if developed in combination with chemotherapy for inoperable and metastatic BCCs. © 2017 Wiley Periodicals, Inc.

Basal cell carcinoma pathogenesis and therapy involving hedgehog signaling and beyond

PubMed Central

Bakshi, Anshika; Chaudhary, Sandeep C.; Rana, Mehtab; Elmets, Craig A.; Athar, Mohammad

2018-01-01

Basal cell carcinoma (BCC) of the skin is driven by aberrant hedgehog signaling. Thus blocking this signaling pathway by small molecules such as vismodegib inhibits tumor growth. Primary cilium in the epidermal cells plays an integral role in the processing of hedgehog signaling-related proteins. Recent genomic studies point to the involvement of additional genetic mutations that might be associated with the development of BCCs, suggesting significance of other signaling pathways, such as WNT, NOTCH, mTOR, and Hippo, aside from hedgehog in the pathogenesis of this human neoplasm. Some of these pathways could be regulated by noncoding microRNA. Altered microRNA expression profile is recognized with the progression of these lesions. Stopping treatment with Smoothened (SMO) inhibitors often leads to tumor reoccurrence in the patients with basal cell nevus syndrome, who develop 10–100 of BCCs. In addition, the initial effectiveness of these SMO inhibitors is impaired due to the onset of mutations in the drug-binding domain of SMO. These data point to a need to develop strategies to overcome tumor recurrence and resistance and to enhance efficacy by developing novel single agent-based or multiple agents-based combinatorial approaches. Immunotherapy and photodynamic therapy could be additional successful approaches particularly if developed in combination with chemotherapy for inoperable and metastatic BCCs. PMID:28574612

Revealing the Molecular Structure and the Transport Mechanism at the Base of Primary Cilia Using Superresolution STED Microscopy

NASA Astrophysics Data System (ADS)

Yang, Tung-Lin

The primary cilium is an organelle that serves as a signaling center of the cell and is involved in the hedgehog signaling, cAMP pathway, Wnt pathways, etc. Ciliary function relies on the transportation of molecules between the primary cilium and the cell, which is facilitated by intraflagellar transport (IFT). IFT88, one of the important IFT proteins in complex B, is known to play a role in the formation and maintenance of cilia in various types of organisms. The ciliary transition zone (TZ), which is part of the gating apparatus at the ciliary base, is home to a large number of ciliopathy molecules. Recent studies have identified important regulating elements for TZ gating in cilia. However, the architecture of the TZ region and its arrangement relative to intraflagellar transport (IFT) proteins remain largely unknown, hindering the mechanistic understanding of the regulation processes. One of the major challenges comes from the tiny volume at the ciliary base packed with numerous proteins, with the diameter of the TZ close to the diffraction limit of conventional microscopes. Using a series of stimulated emission depletion (STED) superresolution images mapped to electron microscopy images, we analyzed the structural organization of the ciliary base. Subdiffraction imaging of TZ components defines novel geometric distributions of RPGRIP1L, MKS1, CEP290, TCTN2 and TMEM67, shedding light on their roles in TZ structure, assembly, and function. We found TCTN2 at the outmost periphery of the TZ close to the ciliary membrane, with a 227+/-18 nm diameter. TMEM67 was adjacent to TCTN2, with a 205+/-20 nm diameter. RPGRIP1L was localized toward the axoneme at the same axial level as TCTN2 and TMEM67, with a 165+/-8 nm diameter. MKS1 was situated between TMEM67 and RPGRIP1L, with an 186+/-21 nm diameter. Surprisingly, CEP290 was localized at the proximal side of the TZ close to the distal end of the centrin-labeled basal body. The lateral width was unexpectedly close to the width of the basal body, distant from the potential Y-links region of the TZ. Moreover, IFT88 was intriguingly distributed in two distinct patterns, forming three puncta or a Y shape at the ciliary base found in human retinal pigment epithelial cells (RPE), human fibroblasts (HFF), mouse inner medullary collecting duct (IMCD) cells and mouse embryonic fibroblasts (MEFs). We hypothesize that the two distribution states of IFT88 correspond to the open and closed gating states of the TZ, where IFT particles aggregate to form three puncta when the gate is closed, and move to form the branches of the Y-shape pattern when the gate is open. Two reservoirs of IFT particles, correlating with phases of ciliary growth, were localized relative to the internal structure of the TZ. These subdiffraction images reveal unprecedented architectural details of the TZ, providing a basic structural framework for future functional studies. To visualize the dynamic movement of IFT particles within primary cilia, we further conducted superresolution live-cell imaging of IFT88 fused to EYFP in IMCD cells. Our findings, in particular, show IFT88 particles pass through the TZ at a reduced speed by approximately 50%, implying the gating mechanism is involved at this region to slow down IFT trafficking. Finally, we report the distinct transport pathways of IFT88 and Smo (Smoothened), an essential player to hedgehog signaling, to support our hypothesis that two proteins are transported in different mechanisms at the ciliary base, based on dual-color superresolution imaging.

Continuity of care: an Italian clinical experience.

PubMed

Tarquini, Roberto; Coletta, Davide; Mazzoccoli, Gianluigi; Gensini, Gian Franco

2013-10-01

Recently, there is a growing interest in the concept of "continuity of care," since patients, being older and more complex, are increasingly seen by an array of providers in a wide variety of organizations and places. Different models of continuity of care have been proposed, yet no single model of care coordination has been proven to be universally applicable across patient (and disease) populations. In the present paper, we introduce a novel model of continuity of care, the Ospedale Santa Verdiana, in Castelfiorentino (Tuscany, Italy), and its first period (1 year) of implementation, since January 2010. There are two main cornerstones: (a) the clinical and urgent need to bridge the gap between primary care and hospital care; and (b) the development and implementation of a model of continuity and coordination of care, which target the so-called complex patient. It is not specific for a single disease but it works "across diseases." There are three driving forces: (a) "primary care" since one of the two Hospital Coordinators is a primary care physician; (b) "hospital care" since patients in the decompensated phase often require hospitalization; and (c) the "University of Florence", which is the "glue". The duties of the Hospital Coordinator, who is an assistant professor at University of Florence, are to guarantee an efficacious and dynamic communication between primary care physicians and hospitalists, and by creating a school for practitioners of the continuity and coordination of care, to make this model exportable.

A Cross-Sectional Comparison of Perceived Quality of Primary Care by Hypertensive Patients in Shanghai and Shenzhen, China

PubMed Central

Li, Haitao; Wei, Xiaolin; Wong, Martin Chi-Sang; Wong, Samuel Yeung-Shan; Yang, Nan; Griffiths, Sian M.

2015-01-01

Abstract Hypertension should be best managed under primary care settings. This study aimed to compare, between Shanghai and Shenzhen, the perceived quality of primary care in terms of accessibility, continuity, co-ordination, and comprehensiveness among hypertensive patients. A cross-sectional study was conducted in Shanghai and Shenzhen, China. Multistage random sampling method was used to select 8 community health centers. Data from primary care users were collected through on-site face-to-face interviews using the primary care assessment tool. Good quality standard was set as a value of 3 for each attribute and a value of 18 for total score. We included 568 patients in Shanghai and 128 patients in Shenzhen. Compared with those in Shenzhen, hypertensive patients in Shanghai reported a higher score in co-ordination of information (3.37 vs 3.66; P < 0.001), but lower scores in continuity of care (3.36 vs 3.27; P < 0.001), and comprehensiveness-service provision (3.26 vs 2.79; P < 0.001). There was no statistically significant difference in total scores between the 2 cities (18.19 vs 18.15). Over 3-quarters of hypertensive patients in both cities reported accessibility (97.2% vs 91.4%) and co-ordination of services (76.1% vs 80.5%) under good quality standard, while <1-quarter of them rated continuity of care (23.6% vs 22.7%), co-ordination of information (4.8% vs 21.1%), and comprehensiveness-service availability (15.1% vs 25.0%) under that standard. Compared with Shenzhen, the perceived quality of primary care for hypertensive patients in Shanghai was better in terms of co-ordination of information, but poorer on continuity of care and comprehensiveness-service provision. Our study suggests that there is room for quality improvement in both cities. PMID:26313780

Function of identified motoneurones and co-ordination of primary and secondary motor systems during zebra fish swimming.

PubMed Central

Liu, D W; Westerfield, M

1988-01-01

1. The activity of the two classes of motoneurones, primary and secondary, which innervate myotomal muscle fibres in the zebra fish, was monitored with electromyographic and intracellular techniques. 2. Simultaneous EMG and intracellular recordings from muscle fibres showed that the activity of the two motor systems and of individual primary motoneurones can be distinguished by recording EMG spikes during swimming. 3. Measurements of EMG spikes demonstrated that primary and secondary motoneurones are co-ordinately activated over a wide range of conditions during normal swimming. 4. During swimming the primary motoneurones within a given segment are usually co-activated although they sometimes fire independently. 5. When different primary motoneurones within a given segment are co-activated, they fire nearly synchronously. 6. We conclude that the primary motoneurones are used principally, although not exclusively, during fast swimming, struggling and the startle response, whereas secondary motoneurones function primarily during slower swimming. PMID:3253426

Evaluating and Terminating Existing Instructional Programs: The Controversial Role of Statewide Coordinating/Governing Agencies.

ERIC Educational Resources Information Center

Johnson, Elizabeth H.

Structures for governing and coordinating higher education are changing. However, the primary responsibility for education rests with the state. The coordinating agency, which occupies the middle-ground between the institutions and the political decision-makers, should have 5 minimum abilities: (1) to engage in continuous planning, both long-range…

Transforming primary care in the New Orleans safety-net: the patient experience.

PubMed

Schmidt, Laura A; Rittenhouse, Diane R; Wu, Kevin J; Wiley, James A

2013-02-01

The patient-centered medical home (PCMH) is a key service delivery innovation in health reform. However, there are growing questions about whether the changes in clinics promoted by the PCMH model lead to improvements in the patient experience. To test the hypothesis that PCMH improvements in safety-net primary care clinics are associated with a more positive patient experience. Multilevel cross-sectional analysis of patients nested within the primary care clinics that serve them. Primary care clinic leaders and patients throughout the City of New Orleans health care safety-net. Dependent variables included patient ratings of accessibility, coordination, and confidence in the quality/safety of care. The key independent variable was a score measuring PCMH structural and process improvements at the clinic level. Approximately two thirds of patients in New Orleans gave positive ratings to their clinics on access and quality/safety, but only one third did for care coordination. In all but the largest clinics, patient experiences of care coordination were positively associated with the clinic's use of PCMH structural and process changes. Results for patient ratings of access and quality/safety were mixed. Among primary care clinics in the New Orleans safety-net, use of more PCMH improvements at the clinic level led to more positive patient rating of care coordination, but not of accessibility or confidence in quality/safety. Ongoing efforts to pilot, demonstrate, implement, and evaluate the PCMH should consider how the impact of medical practice transformation could vary across different aspects of the patient experience.

The intrahepatic signalling niche of hedgehog is defined by primary cilia positive cells during chronic liver injury.

PubMed

Grzelak, Candice Alexandra; Martelotto, Luciano Gastón; Sigglekow, Nicholas David; Patkunanathan, Bramilla; Ajami, Katerina; Calabro, Sarah Ruth; Dwyer, Benjamin James; Tirnitz-Parker, Janina Elke Eleonore; Watkins, D Neil; Warner, Fiona Jane; Shackel, Nicholas Adam; McCaughan, Geoffrey William

2014-01-01

In vertebrates, canonical Hedgehog (Hh) pathway activation requires Smoothened (SMO) translocation to the primary cilium (Pc), followed by a GLI-mediated transcriptional response. In addition, a similar gene regulation occurs in response to growth factors/cytokines, although independently of SMO signalling. The Hh pathway plays a critical role in liver fibrosis/regeneration, however, the mechanism of activation in chronic liver injury is poorly understood. This study aimed to characterise Hh pathway activation upon thioacetamide (TAA)-induced chronic liver injury in vivo by defining Hh-responsive cells, namely cells harbouring Pc and Pc-localised SMO. C57BL/6 mice (wild-type or Ptc1(+/-)) were TAA-treated. Liver injury and Hh ligand/pathway mRNA and protein expression were assessed in vivo. SMO/GLI manipulation and SMO-dependent/independent activation of GLI-mediated transcriptional response in Pc-positive (Pc(+)) cells were studied in vitro. In vivo, Hh activation was progressively induced following TAA. At the epithelial-mesenchymal interface, injured hepatocytes produced Hh ligands. Progenitors, myofibroblasts, leukocytes and hepatocytes were GLI2(+). Pc(+) cells increased following TAA, but only EpCAM(+)/GLI2(+) progenitors were Pc(+)/SMO(+). In vitro, SMO knockdown/hGli3-R overexpression reduced proliferation/viability in Pc(+) progenitors, whilst increased proliferation occurred with hGli1 overexpression. HGF induced GLI transcriptional activity independently of Pc/SMO. Ptc1(+/-) mice exhibited increased progenitor, myofibroblast and fibrosis responses. In chronic liver injury, Pc(+) progenitors receive Hh ligand signals and process it through Pc/SMO-dependent activation of GLI-mediated transcriptional response. Pc/SMO-independent GLI activation likely occurs in Pc(-)/GLI2(+) cells. Increased fibrosis in Hh gain-of-function mice likely occurs by primary progenitor expansion/proliferation and secondary fibrotic myofibroblast expansion, in close contact with progenitors. Copyright © 2013 European Association for the Study of the Liver. All rights reserved.

Mutation of Growth Arrest Specific 8 Reveals a Role in Motile Cilia Function and Human Disease.

PubMed

Lewis, Wesley R; Malarkey, Erik B; Tritschler, Douglas; Bower, Raqual; Pasek, Raymond C; Porath, Jonathan D; Birket, Susan E; Saunier, Sophie; Antignac, Corinne; Knowles, Michael R; Leigh, Margaret W; Zariwala, Maimoona A; Challa, Anil K; Kesterson, Robert A; Rowe, Steven M; Drummond, Iain A; Parant, John M; Hildebrandt, Friedhelm; Porter, Mary E; Yoder, Bradley K; Berbari, Nicolas F

2016-07-01

Ciliopathies are genetic disorders arising from dysfunction of microtubule-based cellular appendages called cilia. Different cilia types possess distinct stereotypic microtubule doublet arrangements with non-motile or 'primary' cilia having a 9+0 and motile cilia have a 9+2 array of microtubule doublets. Primary cilia are critical sensory and signaling centers needed for normal mammalian development. Defects in their structure/function result in a spectrum of clinical and developmental pathologies including abnormal neural tube and limb patterning. Altered patterning phenotypes in the limb and neural tube are due to perturbations in the hedgehog (Hh) signaling pathway. Motile cilia are important in fluid movement and defects in motility result in chronic respiratory infections, altered left-right asymmetry, and infertility. These features are the hallmarks of Primary Ciliary Dyskinesia (PCD, OMIM 244400). While mutations in several genes are associated with PCD in patients and animal models, the genetic lesion in many cases is unknown. We assessed the in vivo functions of Growth Arrest Specific 8 (GAS8). GAS8 shares strong sequence similarity with the Chlamydomonas Nexin-Dynein Regulatory Complex (NDRC) protein 4 (DRC4) where it is needed for proper flagella motility. In mammalian cells, the GAS8 protein localizes not only to the microtubule axoneme of motile cilia, but also to the base of non-motile cilia. Gas8 was recently implicated in the Hh signaling pathway as a regulator of Smoothened trafficking into the cilium. Here, we generate the first mouse with a Gas8 mutation and show that it causes severe PCD phenotypes; however, there were no overt Hh pathway phenotypes. In addition, we identified two human patients with missense variants in Gas8. Rescue experiments in Chlamydomonas revealed a subtle defect in swim velocity compared to controls. Further experiments using CRISPR/Cas9 homology driven repair (HDR) to generate one of these human missense variants in mice demonstrated that this allele is likely pathogenic.

Interventions to improve care coordination between primary healthcare and oncology care providers: a systematic review.

PubMed

Tomasone, Jennifer R; Brouwers, Melissa C; Vukmirovic, Marija; Grunfeld, Eva; O'Brien, Mary Ann; Urquhart, Robin; Walker, Melanie; Webster, Fiona; Fitch, Margaret

2016-01-01

Coordination of patient care between primary care and oncology care providers is vital to care quality and outcomes across the cancer continuum, yet it is known to be challenging. We conducted a systematic review to evaluate current or new models of care and/or interventions aimed at improving coordination between primary care and oncology care providers for patients with adult breast and/or colorectal cancer. MEDLINE, EMBASE, CINAHL, Cochrane Library Database of Systematic Reviews, and the Centre for Reviews and Dissemination were searched for existing English language studies published between January 2000 and 15 May 2015. Systematic reviews, meta-analyses, randomised controlled trials (RCTs) and non-randomised studies were included if they evaluated a specific model/intervention that was designed to improve care coordination between primary care and oncology care providers, for any stage of the cancer continuum, for patients with adult breast and/or colorectal cancer. Two reviewers extracted data and assessed risk of bias. Twenty-two studies (5 systematic reviews, 6 RCTs and 11 non-randomised studies) were included and varied with respect to the targeted phase of the cancer continuum, type of model or intervention tested, and outcome measures. The majority of studies showed no statistically significant changes in any patient, provider or system outcomes. Owing to conceptual and methodological limitations in this field, the review is unable to provide specific conclusions about the most effective or preferred model/intervention to improve care coordination. Imprecise results that lack generalisability and definitiveness provide limited evidence to base the development of future interventions and policies. CRD42015025006.

Data Management Coordinators (DMC)

EPA Pesticide Factsheets

The Regional Data Management Coordinators (DMCs) were identified to serve as the primary contact for each region for all Water Quality Framework activities. They will facilitate and communicate information to the necessary individuals at the region and tra

Implementation of a gerontology nurse specialist role in primary health care: Health professional and older adult perspectives.

PubMed

King, Anna I I; Boyd, Michal L; Dagley, Lynelle; Raphael, Deborah L

2018-02-01

To explore an innovative primary healthcare gerontology nurse specialist role from the perspectives of older people and health professionals. Primary care is struggling to meet the needs and demands of complex older people. New models which incorporate holistic assessment and care coordination are necessary. A qualitative descriptive general inductive design was used. Older people at risk of health and functional decline were identified and received a comprehensive gerontology assessment and care coordination. Older adults (75 years+) enrolled within one of three primary healthcare practices in Auckland, New Zealand were eligible. Healthcare professionals directly involved with the primary healthcare gerontology nurse specialist model were invited for study participation. Face-to-face interviews were held with five older people and six health professionals were interviewed by telephone. A semistructured interview guide was used for all interviews. A general inductive approach was undertaken for analysis to systematically identify codes and themes. Data analysis revealed two central themes from the older people perspective: "holistic expertise" and "communication." Two main themes were identified from the health professional perspective: "competency" and "service delivery." Results showed the gerontology nurse specialist role was highly regarded by both older people and the health professionals. The in-home comprehensive geriatric assessment was identified as greatly beneficial. The competence and care coordination of the gerontology nurse specialist reduced fragmentation and were deemed immensely valuable. Care coordination should be recognised as a key component to meeting the complex needs of at-risk older people in the community. The expert knowledge of the gerontology nurse specialist and in-home comprehensive geriatric assessment were crucial aspects of the new model. Equally important was the assimilation of primary and secondary care infrastructure to upskill and deliver mentorship to the gerontology nurse specialist. © 2017 John Wiley & Sons Ltd.

Coordination of care by primary care practices: strategies, lessons and implications.

PubMed

O'Malley, Ann S; Tynan, Ann; Cohen, Genna R; Kemper, Nicole; Davis, Matthew M

2009-04-01

Despite calls from numerous organizations and payers to improve coordination of care, there are few published accounts of how care is coordinated in real-world primary care practices. This study by the Center for Studying Health System Change (HSC) documents strategies that a range of physician practices use to coordinate care for their patients. While there was no single recipe for coordination given the variety of patient, physician, practice and market factors, some cross-cutting lessons were identified, such as the value of a commitment to interpersonal continuity of care as a foundation for coordination. Respondents also identified the importance of system support for the standardization of office processes to foster care coordination. While larger practices may have more resources to invest, many of the innovations described could be scaled to smaller practices. Some coordination strategies resulted in improved efficiency over time for practices, but by and large, physician practices currently pursue these efforts at their own expense. In addition to sharing information on effective strategies among practices, the findings also provide policy makers with a snapshot of the current care coordination landscape and implications for initiatives to improve coordination. Efforts to provide technical support to practices to improve coordination, for example, through medical-home initiatives, need to consider the baseline more typical practices may be starting from and tailor their support to practices ranging widely in size, resources and presence of standardized care processes. If aligned with payment incentives, some of these strategies have the potential to increase quality and satisfaction among patients and providers by helping to move the health care delivery system toward better coordinated care.

Healthcare provider perceptions of the role of interprofessional care in access to and outcomes of primary care in an underserved area.

PubMed

Wan, Shaowei; Teichman, Peter G; Latif, David; Boyd, Jennifer; Gupta, Rahul

2018-03-01

To meet the needs of an aging population who often have multiple chronic conditions, interprofessional care is increasingly adopted by patient-centred medical homes and Accountable Care Organisations to improve patient care coordination and decrease costs in the United States, especially in underserved areas with primary care workforce shortages. In this cross-sectional survey across multiple clinical settings in an underserved area, healthcare providers perceived overall outcomes associated with interprofessional care teams as positive. This included healthcare providers' beliefs that interprofessional care teams improved patient outcomes, increased clinic efficiency, and enhanced care coordination and patient follow-up. Teams with primary care physician available each day were perceived as better able to coordinate care and follow up with patients (p = .031), while teams that included clinical pharmacists were perceived as preventing medication-associated problems (p < .0001). Healthcare providers perceived the interprofessional care model as a useful strategy to improve various outcomes across different clinical settings in the context of a shortage of primary care physicians.

Mutations in CEP78 Cause Cone-Rod Dystrophy and Hearing Loss Associated with Primary-Cilia Defects.

PubMed

Nikopoulos, Konstantinos; Farinelli, Pietro; Giangreco, Basilio; Tsika, Chrysanthi; Royer-Bertrand, Beryl; Mbefo, Martial K; Bedoni, Nicola; Kjellström, Ulrika; El Zaoui, Ikram; Di Gioia, Silvio Alessandro; Balzano, Sara; Cisarova, Katarina; Messina, Andrea; Decembrini, Sarah; Plainis, Sotiris; Blazaki, Styliani V; Khan, Muhammad Imran; Micheal, Shazia; Boldt, Karsten; Ueffing, Marius; Moulin, Alexandre P; Cremers, Frans P M; Roepman, Ronald; Arsenijevic, Yvan; Tsilimbaris, Miltiadis K; Andréasson, Sten; Rivolta, Carlo

2016-09-01

Cone-rod degeneration (CRD) belongs to the disease spectrum of retinal degenerations, a group of hereditary disorders characterized by an extreme clinical and genetic heterogeneity. It mainly differentiates from other retinal dystrophies, and in particular from the more frequent disease retinitis pigmentosa, because cone photoreceptors degenerate at a higher rate than rod photoreceptors, causing severe deficiency of central vision. After exome analysis of a cohort of individuals with CRD, we identified biallelic mutations in the orphan gene CEP78 in three subjects from two families: one from Greece and another from Sweden. The Greek subject, from the island of Crete, was homozygous for the c.499+1G>T (IVS3+1G>T) mutation in intron 3. The Swedish subjects, two siblings, were compound heterozygotes for the nearby mutation c.499+5G>A (IVS3+5G>A) and for the frameshift-causing variant c.633delC (p.Trp212Glyfs(∗)18). In addition to CRD, these three individuals had hearing loss or hearing deficit. Immunostaining highlighted the presence of CEP78 in the inner segments of retinal photoreceptors, predominantly of cones, and at the base of the primary cilium of fibroblasts. Interaction studies also showed that CEP78 binds to FAM161A, another ciliary protein associated with retinal degeneration. Finally, analysis of skin fibroblasts derived from affected individuals revealed abnormal ciliary morphology, as compared to that of control cells. Altogether, our data strongly suggest that mutations in CEP78 cause a previously undescribed clinical entity of a ciliary nature characterized by blindness and deafness but clearly distinct from Usher syndrome, a condition for which visual impairment is due to retinitis pigmentosa. Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Dynamic Compression of Chondrocyte-Agarose Constructs Reveals New Candidate Mechanosensitive Genes

PubMed Central

Bougault, Carole; Aubert-Foucher, Elisabeth; Paumier, Anne; Perrier-Groult, Emeline; Huot, Ludovic; Hot, David; Duterque-Coquillaud, Martine; Mallein-Gerin, Frédéric

2012-01-01

Articular cartilage is physiologically exposed to repeated loads. The mechanical properties of cartilage are due to its extracellular matrix, and homeostasis is maintained by the sole cell type found in cartilage, the chondrocyte. Although mechanical forces clearly control the functions of articular chondrocytes, the biochemical pathways that mediate cellular responses to mechanical stress have not been fully characterised. The aim of our study was to examine early molecular events triggered by dynamic compression in chondrocytes. We used an experimental system consisting of primary mouse chondrocytes embedded within an agarose hydrogel; embedded cells were pre-cultured for one week and subjected to short-term compression experiments. Using Western blots, we demonstrated that chondrocytes maintain a differentiated phenotype in this model system and reproduce typical chondrocyte-cartilage matrix interactions. We investigated the impact of dynamic compression on the phosphorylation state of signalling molecules and genome-wide gene expression. After 15 min of dynamic compression, we observed transient activation of ERK1/2 and p38 (members of the mitogen-activated protein kinase (MAPK) pathways) and Smad2/3 (members of the canonical transforming growth factor (TGF)-β pathways). A microarray analysis performed on chondrocytes compressed for 30 min revealed that only 20 transcripts were modulated more than 2-fold. A less conservative list of 325 modulated genes included genes related to the MAPK and TGF-β pathways and/or known to be mechanosensitive in other biological contexts. Of these candidate mechanosensitive genes, 85% were down-regulated. Down-regulation may therefore represent a general control mechanism for a rapid response to dynamic compression. Furthermore, modulation of transcripts corresponding to different aspects of cellular physiology was observed, such as non-coding RNAs or primary cilium. This study provides new insight into how chondrocytes respond to mechanical forces. PMID:22615857

Reactive carbonyl compounds impair wound healing by vimentin collapse and loss of the primary cilium.

PubMed

Rodríguez-Ribera, Lara; Slattery, Craig; Mc Morrow, Tara; Marcos, Ricard; Pastor, Susana

2017-10-01

In renal pathologies tubulo-interstitial fibrosis results from an aberrant wound-healing ability where the normal epithelial tissue is substituted for scar tissue caused by accumulation of extracellular matrix proteins (ECM). During the wound-healing process, epithelial cells may undergo epithelial-mesenchymal transition (EMT) acquiring a mesenchymal-like phenotype that allows cells to migrate and re-epithelialize the wound site. It has been reported that chronic inflammation and uremic milieu are involved in wound-healing and enhanced kidney damage in chronic kidney disease (CKD) patients. In this study we evaluated reactive carbonyl compounds (RCC) effects on renal wound healing. The compounds resulting from carbonyl stress evaluated in this study were glyoxal (GO), methylglyoxal (MGO), malondialdehyde (MDA) and 4-hydroxy-hexenal (HHE). Wound repair ability was evaluated by the wound healing assay using HK-2 cells. EMT was evaluated by morphological, protein and transcriptional changes using microscopy, western blot, zymography and RT-qPCR. Changes in the vimentin network and primary cilia were assessed by immunofluorescence. Our data demonstrated that MDA and GO delay wound closure mediated by vimentin disruption, which caused collagen I mRNA decrease, and deciliation. In contrast, HHE treatment (and MGO to a minor degree) induced morphological changes and increased mesenchymal marker expression and gelatinase activity in HK-2 cells. In this study, we have demonstrated for the first time that exposure to RCC differentially affects wound healing in proximal tubular epithelia. A better comprehension of effects of uremic toxins on wound healing and fibrosis and migration is necessary to seek mechanisms to slow down renal fibrosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Development of a web-based toolkit to support improvement of care coordination in primary care.

PubMed

Ganz, David A; Barnard, Jenny M; Smith, Nina Z Y; Miake-Lye, Isomi M; Delevan, Deborah M; Simon, Alissa; Rose, Danielle E; Stockdale, Susan E; Chang, Evelyn T; Noël, Polly H; Finley, Erin P; Lee, Martin L; Zulman, Donna M; Cordasco, Kristina M; Rubenstein, Lisa V

2018-05-23

Promising practices for the coordination of chronic care exist, but how to select and share these practices to support quality improvement within a healthcare system is uncertain. This study describes an approach for selecting high-quality tools for an online care coordination toolkit to be used in Veterans Health Administration (VA) primary care practices. We evaluated tools in three steps: (1) an initial screening to identify tools relevant to care coordination in VA primary care, (2) a two-clinician expert review process assessing tool characteristics (e.g. frequency of problem addressed, linkage to patients' experience of care, effect on practice workflow, and sustainability with existing resources) and assigning each tool a summary rating, and (3) semi-structured interviews with VA patients and frontline clinicians and staff. Of 300 potentially relevant tools identified by searching online resources, 65, 38, and 18 remained after steps one, two and three, respectively. The 18 tools cover five topics: managing referrals to specialty care, medication management, patient after-visit summary, patient activation materials, agenda setting, patient pre-visit packet, and provider contact information for patients. The final toolkit provides access to the 18 tools, as well as detailed information about tools' expected benefits, and resources required for tool implementation. Future care coordination efforts can benefit from systematically reviewing available tools to identify those that are high quality and relevant.

Views of Dental Providers on Primary Care Coordination at Chairside: A Pilot Study.

PubMed

Northridge, Mary E; Birenz, Shirley; Gomes, Danni M; Golembeski, Cynthia A; Greenblatt, Ariel Port; Shelley, Donna; Russell, Stefanie L

2016-06-01

There is a need for research to facilitate the widespread implementation, dissemination and sustained utilization of evidence-based primary care screening, monitoring and care coordination guidelines, thereby increasing the impact of dental hygienists' actions on patients' oral and general health. The aims of this formative study are to explore dental hygienists' and dentists' perspectives regarding the integration of primary care activities into routine dental care, and assess the needs of dental hygienists and dentists regarding primary care coordination activities and use of information technology to obtain clinical information at chairside. This qualitative study recruited 10 dental hygienists and 6 dentists from 10 New York City area dental offices with diverse patient mixes and volumes. A New York University faculty dental hygienist conducted semi-structured, in-depth interviews, which were digitally recorded and transcribed verbatim. Data analysis consisted of multilevel coding based on the Consolidated Framework for Implementation Research, resulting in emergent themes with accompanying categories. The dental hygienists and dentists interviewed as part of this study do not use evidence-based guidelines to screen their patients for primary care sensitive conditions. Overwhelmingly, dental providers believe that tobacco use and poor diet contribute to oral disease, and report using electronic devices at chairside to obtain web-based health information. Dental hygienists are well positioned to help facilitate greater integration of oral and general health care. Challenges include lack of evidence-based knowledge, coordination between dental hygienists and dentists, and systems-level support, with opportunities for improvement based upon a theory-driven framework. Copyright © 2016 The American Dental Hygienists’ Association.

Views of Dental Providers on Primary Care Coordination at Chairside: A Pilot Study

PubMed Central

Northridge, Mary E.; Birenz, Shirley; Gomes, Danni; Golembeski, Cynthia A.; Greenblatt, Ariel Port; Shelley, Donna; Russell, Stefanie L.

2016-01-01

Purpose There is a need for research to facilitate the widespread implementation, dissemination, and sustained utilization of evidence-based primary care screening, monitoring, and care coordination guidelines, thereby increasing the impact of dental hygienists’ actions on patients’ oral and general health. The aims of this formative study are to: (1) explore dental hygienists’ and dentists’ perspectives regarding the integration of primary care activities into routine dental care; and (2) assess the needs of dental hygienists and dentists regarding primary care coordination activities and use of information technology to obtain clinical information at chairside. Methods This qualitative study recruited ten hygienists and six dentists from ten New York City area dental offices with diverse patient mixes and volumes. A New York University faculty hygienist conducted semi-structured, in-depth interviews, which were digitally recorded and transcribed verbatim. Data analysis consisted of multilevel coding based on the Consolidated Framework for Implementation Research, resulting in emergent themes with accompanying categories. Results The dental hygienists and dentists interviewed as part of this study fail to use evidence-based guidelines to screen their patients for primary care sensitive conditions. Overwhelmingly, dental providers believe that tobacco use and poor diet contribute to oral disease, and report using electronic devices at chairside to obtain web-based health information. Conclusion Dental hygienists are well positioned to help facilitate greater integration of oral and general health care. Challenges include lack of evidence-based knowledge, coordination between dental hygienists and dentists, and systems-level support, with opportunities for improvement based upon a theory-driven framework. PMID:27340183

Care coordination in primary health care: an evaluative study in a municipality in the Northeast of Brazil.

PubMed

Aleluia, Italo Ricardo Santos; Medina, Maria Guadalupe; Almeida, Patty Fidelis de; Vilasbôas, Ana Luiza Queiroz

2017-06-01

International and Brazilian studies have highlighted the importance of the coordination of care for the organization of local health systems. This study aimed to analyze the coordination of care by Primary Health Care (PHC) in a municipal health system in the State of Bahia. This study was conducted in the lead municipality of the macro-region and involved two levels of analysis: PHC team and municipal management. Outlining conditions for the study were defined (hypertension and diabetes mellitus) and an objective image corresponding to the coordination of care was developed based on current national and international literature review. Semi-structured interviews with professionals, managers of PHC services were conducted and current documentary sources were also used. It was demonstrated that the coordination of care has not been met by municipal systems, where only 14 of the 22 proposed criteria have been met. The main difficulties and reasons were: a lack of health care protocols and the non-implementation of computer systems and telecommunication technologies. The results and the conceptual framework to assess the coordination of care are relevant contributions to this study, which can be applied to other contexts with similar characteristics.

42 CFR 440.168 - Primary care case management services.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 4 2010-10-01 2010-10-01 false Primary care case management services. 440.168... care case management services. (a) Primary care case management services means case management related services that— (1) Include location, coordination, and monitoring of primary health care services; and (2...

42 CFR 440.168 - Primary care case management services.

Code of Federal Regulations, 2014 CFR

2014-10-01

... care case management services. (a) Primary care case management services means case management related services that— (1) Include location, coordination, and monitoring of primary health care services; and (2... 42 Public Health 4 2014-10-01 2014-10-01 false Primary care case management services. 440.168...

42 CFR 440.168 - Primary care case management services.

Code of Federal Regulations, 2011 CFR

2011-10-01

... care case management services. (a) Primary care case management services means case management related services that— (1) Include location, coordination, and monitoring of primary health care services; and (2... 42 Public Health 4 2011-10-01 2011-10-01 false Primary care case management services. 440.168...

42 CFR 440.168 - Primary care case management services.

Code of Federal Regulations, 2012 CFR

2012-10-01

... care case management services. (a) Primary care case management services means case management related services that— (1) Include location, coordination, and monitoring of primary health care services; and (2... 42 Public Health 4 2012-10-01 2012-10-01 false Primary care case management services. 440.168...

42 CFR 440.168 - Primary care case management services.

Code of Federal Regulations, 2013 CFR

2013-10-01

... care case management services. (a) Primary care case management services means case management related services that— (1) Include location, coordination, and monitoring of primary health care services; and (2... 42 Public Health 4 2013-10-01 2013-10-01 false Primary care case management services. 440.168...

Perioperative Care Coordination Measurement: A Tool to Support Care Integration of Pediatric Surgical Patients.

PubMed

Ferrari, Lynne R; Ziniel, Sonja I; Antonelli, Richard C

2016-03-01

The relationship of care coordination activities and outcomes to resource utilization and personnel costs has been evaluated for a number of pediatric medical home practices. One of the first tools designed to evaluate the activities and outcomes for pediatric care coordination is the Care Coordination Measurement Tool (CCMT). It has become widely used as an instrument for health care providers in both primary and subspecialty care settings. This tool enables the user to stratify patients based on acuity and complexity while documenting the activities and outcomes of care coordination. We tested the feasibility of adapting the CCMT to a pediatric surgical population at Boston Children's Hospital. The tool was used to assess the preoperative care coordination activities. Care coordination activities were tracked during the interval from the date the patient was scheduled for a surgical or interventional procedure through the day of the procedure. A care coordination encounter was defined as any task, whether face to face or not, supporting the development or implementation of a plan of care. Data were collected to enable analysis of 5675 care coordination encounters supporting the care provided to 3406 individual surgical cases (patients). The outcomes of care coordination, as documented by the preoperative nursing staff, included the elaboration of the care plan through patient-focused communication among specialist, facilities, perioperative team, and primary care physicians in 80.5% of cases. The average time spent on care coordination activities increased incrementally by 30 minutes with each additional care coordination encounter for a surgical case. Surgical cases with 1 care coordination encounter took an average of 35.7 minutes of preoperative care coordination, whereas those with ≥4 care coordination encounters reported an average of 121.6 minutes. We successfully adapted and implemented the CCMT for a pediatric surgical population and measured nonface-to-face, nonbillable encounters performed by perioperative nursing staff. The care coordination activities integrated into the preoperative process include elaboration of care plans and identification and remediation of discrepancies. Capturing the activities and outcomes of care coordination for preoperative care provides a framework for quality improvement and enables documentation of the value of nonface-to-face perioperative nursing encounters that comprise care coordination.

Usher syndrome: animal models, retinal function of Usher proteins, and prospects for gene therapy

PubMed Central

Williams, David S.

2009-01-01

Usher syndrome is a deafness-blindness disorder. The blindness occurs from a progressive retinal degeneration that begins after deafness and after the retina has developed. Three clinical subtypes of Usher syndrome have been identified, with mutations in any one of six different genes giving rise to type 1, in any one of three different genes to type 2, and in one identified gene causing Usher type 3. Mutant mice for most of the genes have been studied; while they have clear inner ear defects, retinal phenotypes are relatively mild and have been difficult to characterize. The retinal functions of the Usher proteins are still largely unknown. Protein binding studies have suggested many interactions among the proteins, and a model of interaction among all the proteins in the photoreceptor synapse has been proposed. However this model is not supported by localization data from some laboratories, or the indication of any synaptic phenotype in mutant mice. An earlier suggestion, based on patient pathologies, of Usher protein function in the photoreceptor cilium continues to gain support from immunolocalization and mutant mouse studies, which are consistent with Usher protein interaction in the photoreceptor ciliary/periciliary region. So far, the most characterized Usher protein is myosin VIIa. It is present in the apical RPE and photoreceptor ciliary/periciliary region, where it is required for organelle transport and clearance of opsin from the connecting cilium, respectively. Usher syndrome is amenable to gene replacement therapy, but also has some specific challenges. Progress in this treatment approach has been achieved by correction of mutant phenotypes in Myo7a-null mouse retinas, following lentiviral delivery of MYO7A. PMID:17936325

Arima syndrome caused by CEP290 specific variant and accompanied with pathological cilium; clinical comparison with Joubert syndrome and its related diseases.

PubMed

Itoh, Masayuki; Ide, Shuhei; Iwasaki, Yuji; Saito, Takashi; Narita, Keishi; Dai, Hongmei; Yamakura, Shinji; Furue, Takeki; Kitayama, Hirotsugu; Maeda, Keiko; Takahashi, Eihiko; Matsui, Kiyoshi; Goto, Yu-Ichi; Takeda, Sen; Arima, Masataka

2018-04-01

Arima syndrome (AS) is a rare disease and its clinical features mimic those of Joubert syndrome or Joubert syndrome-related diseases (JSRD). Recently, we clarified the AS diagnostic criteria and its severe phenotype. However, genetic evidence of AS remains unknown. We explored causative genes of AS and compared the clinical and genetic features of AS with the other JSRD. We performed genetic analyses of 4 AS patients of 3 families with combination of whole-exome sequencing and Sanger sequencing. Furthermore, we studied cell biology with the cultured fibroblasts of 3 AS patients. All patients had a specific homozygous variant (c.6012-12T>A, p.Arg2004Serfs*7) or compound heterozygous variants (c.1711+1G>A; c.6012-12T>A, p.Gly570Aspfs*19;Arg2004Serfs*7) in centrosomal protein 290 kDa (CEP290) gene. These unique variants lead to abnormal splicing and premature termination. Morphological analysis of cultured fibroblasts from AS patients revealed a marked decrease of the CEP290-positive cell number with significantly longer cilium and naked and protruded ciliary axoneme without ciliary membrane into the cytoplasm. AS resulted in cilia dysfunction from centrosome disruption. The unique variant of CEP290 could be strongly linked to AS pathology. Here, we provided AS specific genetic evidence, which steers the structure and functions of centrosome that is responsible for normal ciliogenesis. This is the first report that has demonstrated the molecular basis of Arima syndrome. Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Turning on the care coordination switch in rural primary care: voices from the practices--clinician champions, clinician partners, administrators, and nurse care managers.

PubMed

Fagnan, Lyle J; Dorr, David A; Davis, Melinda; McGinnis, Paul; Mahler, Jo; King, Molly McCarthy; Michaels, LeAnn

2011-01-01

This study sought to understand the acceptability and feasibility of office-based nurse care management in medium to large rural primary care practices. A qualitative assessment of Care Management Plus (a focused medical home model for complex patients) implementation was conducted using semistructured interviews with 4 staff cohorts. Cohorts included clinician champions, clinician partners, practice administrators, and nurse care managers. Seven key implementation attributes were: a proven care coordination program; adequate staffing; practice buy-in; adequate time; measurement; practice facilitation; and functional information technology. Although staff was positive about the care coordination concept, model acceptability was varied and additional study is required to determine sustainability.

Results of a coordination and shared clinical information programme between primary care and nephrology.

PubMed

García García, Manuel; Valenzuela Mújica, Mari Pau; Martínez Ocaña, Juan Carlos; Otero López, María del Sol; Ponz Clemente, Esther; López Alba, Thaïs; Gálvez Hernández, Enrique

2011-01-01

The high prevalence of chronic kidney disease (CKD) in the general population has created a need to coordinate specialised nephrology care and primary care. Although several systems have been developed to coordinate this process, published results are scarce and contradictory. To present the results of the application of a coordinated programme between nephrology care and primary care through consultations and a system of shared clinical information to facilitate communication and improve the criteria for referring patients. Elaboration of a coordinated care programme by the primary care management team and the nephrology department, based on the SEN-SEMFYC consensus document and a protocol for the study and management of arterial hypertension (AHT). Explanation and implementation in primary health care units. A directory of specialists’ consultations was created, both in-person and via e-mail. A continuous training programme in kidney disease and arterial hypertension was implemented in the in-person consultation sessions. The programme was progressively implemented over a three-year period (2007-2010) in an area of 426,000 inhabitants with 230 general practitioners. Use of a clinical information system named Salut en Xarxa that allows access to clinical reports, diagnoses, prescriptions, test results and clinical progression. Improved referral criteria between primary care and specialised nephrology service. Improved prioritisation of visits. Progressive increase in referrals denied by specialists (28.5% in 2009), accompanied by an explanatory report including suggestions for patient management. Decrease in first nephrology outpatient visits that have been referred from primary care (15% in 2009). Family doctors were generally satisfied with the improvement in communication and the continuous training programme. The main causes for denying referral requests were: patients >70 years with stage 3 CKD (44.15%); patients <70 years with stage 3a CKD (19.15%); albumin/creatinine ratio <500 mg/g (12.23%); non-secondary, non-refractory, essential AHT (11.17%). The general practitioners included in the programme showed great interest and no complaints were registered. The consultations improve adequacy and prioritisation of nephrology visits, allow for better communication between different levels of the health system, and offer systematic training for general practitioners to improve the management of nephrology patients. This process allows for referring nephrology patients with the most complex profiles to nephrology outpatient clinics.

32 CFR 153.4 - Responsibilities.

Code of Federal Regulations, 2013 CFR

2013-07-01

... General Counsel of the Department of Defense shall provide initial coordination and liaison with the... lead to successful prosecutions and, therefore, these cases warrant close coordination and cooperation... primary point of contact for DoD personnel regarding all investigations that may lead to criminal...

32 CFR 153.4 - Responsibilities.

Code of Federal Regulations, 2014 CFR

2014-07-01

... General Counsel of the Department of Defense shall provide initial coordination and liaison with the... lead to successful prosecutions and, therefore, these cases warrant close coordination and cooperation... primary point of contact for DoD personnel regarding all investigations that may lead to criminal...

32 CFR 153.4 - Responsibilities.

Code of Federal Regulations, 2011 CFR

2011-07-01

... General Counsel of the Department of Defense shall provide initial coordination and liaison with the... lead to successful prosecutions and, therefore, these cases warrant close coordination and cooperation... primary point of contact for DoD personnel regarding all investigations that may lead to criminal...

32 CFR 153.4 - Responsibilities.

Code of Federal Regulations, 2012 CFR

2012-07-01

... General Counsel of the Department of Defense shall provide initial coordination and liaison with the... lead to successful prosecutions and, therefore, these cases warrant close coordination and cooperation... primary point of contact for DoD personnel regarding all investigations that may lead to criminal...

Acute Lung Injury: Making Injured Lungs Perform Better and Rebuilding Healthy Lungs

DTIC Science & Technology

2010-07-01

Informed consent will be obtained by the study coordinator/respiratory therapist from legally authorized representatives (defined as a subject’s...will be identified by the primary intensive care unit team, who will notify the study coordinator/respiratory therapist . The study coordinator is a...registered respiratory therapist with human subjects research training and qualifications for obtaining consent, clinical monitoring, arterial blood

Whole exome sequencing is an efficient, sensitive and specific method for determining the genetic cause of short-rib thoracic dystrophies.

PubMed

McInerney-Leo, A M; Harris, J E; Leo, P J; Marshall, M S; Gardiner, B; Kinning, E; Leong, H Y; McKenzie, F; Ong, W P; Vodopiutz, J; Wicking, C; Brown, M A; Zankl, A; Duncan, E L

2015-12-01

Short-rib thoracic dystrophies (SRTDs) are congenital disorders due to defects in primary cilium function. SRTDs are recessively inherited with mutations identified in 14 genes to date (comprising 398 exons). Conventional mutation detection (usually by iterative Sanger sequencing) is inefficient and expensive, and often not undertaken. Whole exome massive parallel sequencing has been used to identify new genes for SRTD (WDR34, WDR60 and IFT172); however, the clinical utility of whole exome sequencing (WES) has not been established. WES was performed in 11 individuals with SRTDs. Compound heterozygous or homozygous mutations were identified in six confirmed SRTD genes in 10 individuals (IFT172, DYNC2H1, TTC21B, WDR60, WDR34 and NEK1), giving overall sensitivity of 90.9%. WES data from 993 unaffected individuals sequenced using similar technology showed two individuals with rare (minor allele frequency <0.005) compound heterozygous variants of unknown significance in SRTD genes (specificity >99%). Costs for consumables, laboratory processing and bioinformatic analysis were

Centrosomal protein Dzip1l binds Cby, promotes ciliary bud formation, and acts redundantly with Bromi to regulate ciliogenesis in the mouse.

PubMed

Wang, Chengbing; Li, Jia; Takemaru, Ken-Ichi; Jiang, Xiaogang; Xu, Guoqiang; Wang, Baolin

2018-03-15

The primary cilium is a microtubule-based organelle required for Hedgehog (Hh) signaling and consists of a basal body, a ciliary axoneme and a compartment between the first two structures, called the transition zone (TZ). The TZ serves as a gatekeeper to control protein composition in cilia, but less is known about its role in ciliary bud formation. Here, we show that centrosomal protein Dzip1l is required for Hh signaling between Smoothened and Sufu. Dzip1l colocalizes with basal body appendage proteins and Rpgrip1l, a TZ protein. Loss of Dzip1l results in reduced ciliogenesis and dysmorphic cilia in vivo Dzip1l interacts with, and acts upstream of, Cby, an appendage protein, in ciliogenesis. Dzip1l also has overlapping functions with Bromi (Tbc1d32) in ciliogenesis, cilia morphogenesis and neural tube patterning. Loss of Dzip1l arrests ciliogenesis at the stage of ciliary bud formation from the TZ. Consistent with this, Dzip1l mutant cells fail to remove the capping protein Cp110 (Ccp110) from the distal end of mother centrioles and to recruit Rpgrip1l to the TZ. Therefore, Dzip1l promotes ciliary bud formation and is required for the integrity of the TZ. © 2018. Published by The Company of Biologists Ltd.

Auditory hair cell centrioles undergo confined Brownian motion throughout the developmental migration of the kinocilium.

PubMed

Lepelletier, Léa; de Monvel, Jacques Boutet; Buisson, Johanna; Desdouets, Chantal; Petit, Christine

2013-07-02

Planar polarization of the forming hair bundle, the mechanosensory antenna of auditory hair cells, depends on the poorly characterized center-to-edge displacement of a primary cilium, the kinocilium, at their apical surface. Taking advantage of the gradient of hair cell differentiation along the cochlea, we reconstituted a map of the kinocilia displacements in the mouse embryonic cochlea. We then developed a cochlear organotypic culture and video-microscopy approach to monitor the movements of the kinocilium basal body (mother centriole) and its daughter centriole, which we analyzed using particle tracking and modeling. We found that both hair cell centrioles undergo confined Brownian movements around their equilibrium positions, under the apparent constraint of a radial restoring force of ∼0.1 pN. This magnitude depended little on centriole position, suggesting nonlinear interactions with constraining, presumably cytoskeletal elements. The only dynamic change observed during the period of kinocilium migration was a doubling of the centrioles' confinement area taking place early in the process. It emerges from these static and dynamic observations that kinocilia migrate gradually in parallel with the organization of hair cells into rows during cochlear neuroepithelium extension. Analysis of the confined motion of hair cell centrioles under normal and pathological conditions should help determine which structures contribute to the restoring force exerting on them. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Mutations in human C2CD3 cause skeletal dysplasia and provide new insights into phenotypic and cellular consequences of altered C2CD3 function

PubMed Central

Cortés, Claudio R.; McInerney-Leo, Aideen M.; Vogel, Ida; Rondón Galeano, Maria C.; Leo, Paul J.; Harris, Jessica E.; Anderson, Lisa K.; Keith, Patricia A.; Brown, Matthew A.; Ramsing, Mette; Duncan, Emma L.; Zankl, Andreas; Wicking, Carol

2016-01-01

Ciliopathies are a group of genetic disorders caused by defective assembly or dysfunction of the primary cilium, a microtubule-based cellular organelle that plays a key role in developmental signalling. Ciliopathies are clinically grouped in a large number of overlapping disorders, including the orofaciodigital syndromes (OFDS), the short rib polydactyly syndromes and Jeune asphyxiating thoracic dystrophy. Recently, mutations in the gene encoding the centriolar protein C2CD3 have been described in two families with a new sub-type of OFDS (OFD14), with microcephaly and cerebral malformations. Here we describe a third family with novel compound heterozygous C2CD3 mutations in two fetuses with a different clinical presentation, dominated by skeletal dysplasia with no microcephaly. Analysis of fibroblast cultures derived from one of these fetuses revealed a reduced ability to form cilia, consistent with previous studies in C2cd3-mutant mouse and chicken cells. More detailed analyses support a role for C2CD3 in basal body maturation; but in contrast to previous mouse studies the normal recruitment of the distal appendage protein CEP164 suggests that this protein is not sufficient for efficient basal body maturation and subsequent axonemal extension in a C2CD3-defective background. PMID:27094867

Auditory Hair Cell Centrioles Undergo Confined Brownian Motion Throughout the Developmental Migration of the Kinocilium

PubMed Central

Lepelletier, Léa; de Monvel, Jacques Boutet; Buisson, Johanna; Desdouets, Chantal; Petit, Christine

2013-01-01

Planar polarization of the forming hair bundle, the mechanosensory antenna of auditory hair cells, depends on the poorly characterized center-to-edge displacement of a primary cilium, the kinocilium, at their apical surface. Taking advantage of the gradient of hair cell differentiation along the cochlea, we reconstituted a map of the kinocilia displacements in the mouse embryonic cochlea. We then developed a cochlear organotypic culture and video-microscopy approach to monitor the movements of the kinocilium basal body (mother centriole) and its daughter centriole, which we analyzed using particle tracking and modeling. We found that both hair cell centrioles undergo confined Brownian movements around their equilibrium positions, under the apparent constraint of a radial restoring force of ∼0.1 pN. This magnitude depended little on centriole position, suggesting nonlinear interactions with constraining, presumably cytoskeletal elements. The only dynamic change observed during the period of kinocilium migration was a doubling of the centrioles’ confinement area taking place early in the process. It emerges from these static and dynamic observations that kinocilia migrate gradually in parallel with the organization of hair cells into rows during cochlear neuroepithelium extension. Analysis of the confined motion of hair cell centrioles under normal and pathological conditions should help determine which structures contribute to the restoring force exerting on them. PMID:23823223

Suppressor of Fused Chaperones Gli Proteins To Generate Transcriptional Responses to Sonic Hedgehog Signaling

PubMed Central

Zhang, Ziyu; Shen, Longyan; Law, Kelvin; Zhang, Zengdi; Liu, Xiaotong; Hua, Hu; Li, Sanen; Huang, Huijie; Yue, Shen; Hui, Chi-chung

2016-01-01

ABSTRACT Cellular responses to the graded Sonic Hedgehog (Shh) morphogenic signal are orchestrated by three Gli genes that give rise to both transcription activators and repressors. An essential downstream regulator of the pathway, encoded by the tumor suppressor gene Suppressor of fused (Sufu), plays critical roles in the production, trafficking, and function of Gli proteins, but the mechanism remains controversial. Here, we show that Sufu is upregulated in active Shh responding tissues and accompanies Gli activators translocating into and Gli repressors out of the nucleus. Trafficking of Sufu to the primary cilium, potentiated by Gli activators but not repressors, was found to be coupled to its nuclear import. We have identified a nuclear export signal (NES) motif of Sufu in juxtaposition to the protein kinase A (PKA) and glycogen synthase kinase 3 (GSK3) dual phosphorylation sites and show that Sufu binds the chromatin with both Gli1 and Gli3. Close comparison of neural tube development among individual Ptch1−/−, Sufu−/−, and Ptch1−/−; Sufu−/− double mutant embryos indicates that Sufu is critical for the maximal activation of Shh signaling essential to the specification of the most-ventral neurons. These data define Sufu as a novel class of molecular chaperone required for every aspect of Gli regulation and function. PMID:27849569

Counselling in Primary Care: Past, Present, and Future.

ERIC Educational Resources Information Center

Eatock, John

2000-01-01

Presents a brief history of the growth of counseling in primary care. Discusses the challenges for primary care counselors and counseling, as well as the need for coordination, regulation and management. Also discusses the imperative for research support and the unique nature of counseling in primary care including challenges to its survival. (MKA)

Elements of the patient-centered medical home associated with health outcomes among veterans: the role of primary care continuity, expanded access, and care coordination.

PubMed

Nelson, Karin; Sun, Haili; Dolan, Emily; Maynard, Charles; Beste, Laruen; Bryson, Christopher; Schectman, Gordon; Fihn, Stephan D

2014-01-01

Care continuity, access, and coordination are important features of the patient-centered medical home model and have been emphasized in the Veterans Health Administration patient-centered medical home implementation, called the Patient Aligned Care Team. Data from more than 4.3 million Veterans were used to assess the relationship between these attributes of Patient Aligned Care Team and Veterans Health Administration hospitalization and mortality. Controlling for demographics and comorbidity, we found that continuity with a primary care provider was associated with a lower likelihood of hospitalization and mortality among a large population of Veterans receiving VA primary care.

Why primary care practices should become digital health information hubs for their patients.

PubMed

Baird, Aaron; Nowak, Samantha

2014-11-25

Two interesting health care trends are currently occurring: 1) patient-facing technologies, such as personal health records, patient portals, and mobile health apps, are being adopted at rapid rates, and 2) primary care, which includes family practice, is being promoted as essential to reducing health care costs and improving health care outcomes. While these trends are notable and commendable, both remain subject to significant fragmentation and incentive misalignments, which has resulted in significant data coordination and value generation challenges. In particular, patient-facing technologies designed to increase care coordination, often fall prey to the very digital fragmentation issues they are supposed to overcome. Additionally, primary care providers are treating patients that may have considerable health information histories, but generating a single view of such multi-source data is nearly impossible. We contribute to this debate by proposing that primary care practices become digital health information hubs for their patients. Such hubs would offer health data coordination in a medically professional setting with the benefits of expert, trustworthy advice coupled with active patient engagement. We acknowledge challenges including: costs, information quality and provenance, willingness-to-share information and records, willingness-to-use (by both providers and patients), primary care scope creep, and determinations of technical and process effectiveness. Even with such potential challenges, we strongly believe that more debate is needed on this topic prior to full implementation of various health information technology incentives and reform programs currently being designed and enacted throughout the world. Ultimately, if we do not provide a meaningful way for the full spectrum of health information to be used by both providers and patients, especially early in the health care continuum, effectively improving health outcomes may remain elusive. We view the primary care practice as a central component of digital information coordination, especially when considering the current challenges of digital health information fragmentation. Given these fragmentation issues and the emphasis on primary care as central to improving health and lower overall health care costs, we suggest that primary care practices should embrace their evolving role and should seek to become digital health information hubs for their patients.

The Perceived Impact of 42 CFR Part 2 on Coordination and Integration of Care: A Qualitative Analysis.

PubMed

McCarty, Dennis; Rieckmann, Traci; Baker, Robin L; McConnell, K John

2017-03-01

Title 42 of the Code of Federal Regulations Part 2 (42 CFR Part 2) controls the release of patient information about treatment for substance use disorders. In 2016, the Substance Abuse and Mental Health Services Administration (SAMHSA) released a proposed rule to update the regulations, reduce provider burdens, and facilitate information exchange. Oregon's Medicaid program (Oregon Health Plan) altered the financing and structure of medical, dental, and behavioral care to promote greater integration and coordination. A qualitative analysis examined the perceived impact of 42 CFR Part 2 on care coordination and integration. Interviews with 76 stakeholders (114 interviews) conducted in 2012-2015 probed the processes of integrating behavioral health into primary care settings in Oregon and assessed issues associated with adherence to 42 CFR Part 2. Respondents expressed concerns that the regulations caused legal confusion, inhibited communication and information sharing, and required updating. Addiction treatment directors noted the challenges of obtaining patient consent to share information with primary care providers. The confidentiality regulations were perceived as a barrier to care coordination and integration. The Oregon Health Authority, therefore, requested regulatory changes. SAMHSA's proposed revisions permit a general consent to an entire health care team and allow inclusion of substance use disorder information within health information exchanges, but they mandate data segmentation of diagnostic and procedure codes related to substance use disorders and restrict access only to parties with authorized consent, possibly adding barriers to the coordination and integration of addiction treatment with primary care.

The effect of a nurse-led telephone-based care coordination program on the follow-up and control of cardiovascular risk factors in patients with coronary artery disease.

PubMed

Wong, Ningyan; Chua, Siang Jin Terrance; Gao, Fei; Sim, Sok Tiang Rosalind; Matchar, David; Wong, Sung Lung Aaron; Yeo, Khung Keong; Tan, Wei Chieh Jack; Chin, Chee Tang

2016-12-01

We sought to analyse the impact of a care coordination protocol on transiting patients with coronary artery disease who had undergone percutaneous coronary intervention (PCI) to primary care and its effect on cardiovascular risk factor control. A prospective observational study involving 492 patients who had undergone PCI either electively or after an acute coronary syndrome. A tertiary institution in Singapore. Patients who had undergone a PCI either electively or after an acute coronary syndrome. The SCORE (Standardized Care for Optimal Outcomes, Right-Siting and Rapid Re-evaluation) program was a nurse-led, telephone-based, care coordination protocol. Transition to primary care within 1 year of enrolment, the achievement of low-density lipoprotein (LDL) level of <2.6 mmol/l within 1 year and hospital admissions related to cardiovascular causes within 1 year were studied. Under the SCORE protocol, a significantly higher number of patients transited to primary care and achieved the LDL target within 1 year, as compared with non-SCORE patients. Discharge to primary care and achievement of target LDL continued to be higher among those under the SCORE protocol even after multivariate analysis. Rates of hospital admission due to cardiovascular causes were not significantly different. Care coordination improved the rate of transition of post-PCI patients to primary care and improved LDL control, with no difference in the rate of hospital admissions due to cardiovascular causes. These findings support the implementation of a standardized follow-up protocol in patients who have undergone PCI. © The Author 2016. Published by Oxford University Press in association with the International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Novel, posterior sensory organ in the trochophore larva of Phyllodoce maculata (Polychaeta).

PubMed Central

Nezlin, L P; Voronezhskaya, E E

2003-01-01

A new posterior sensory organ (PSO), located at the dorsal midline of the hyposphere, is described by immunocytochemical detection of acetylated alpha tubulin and serotonin (5-HT) in a laser-scanning microscope, as well as three-dimensional reconstructions after optical serial sectioning in the trochophore larva of the polychaete Phyllodoce maculata (Phyllodocidae). The unpaired PSO consists of five bipolar sensory cells, two of them being 5-HT immunopositive, which send axons to the cerebral ganglion and prototroch nerve. The dendrites of these cells project to the surface and bear one cilium each. A single neuronal fibre from the apical sensory organ innervates the PSO. PMID:14667369

Ultrastructural observations of the larva of Tubiluchus corallicola (Priapulida)

NASA Astrophysics Data System (ADS)

Higgins, R. P.; Storch, V.

1989-03-01

Larvae of Tubiluchus corallicola van der Land 1968 were investigated by scanning and transmission electron microscopy. The scalids are sensory organs, each has a bipolar receptor cell with a single apical cilium similar to the scalid in the adult. Muscle cells of the larva are more differentiated than previously reported for other Priapulida; the larval arrangement of circular and longitudinal musculature differs from that of the adult, and a diaphragm is reported for the first time in Priapulida. The diaphragm may function in hydrostatic control of eversion and inversion of the introvert and mouth cone. The functional morphology of these two structures is discussed and contrasted with the Kinorhyncha.

The association between EHRs and care coordination varies by team cohesion.

PubMed

Graetz, Ilana; Reed, Mary; Shortell, Stephen M; Rundall, Thomas G; Bellows, Jim; Hsu, John

2014-02-01

To examine whether primary care team cohesion changes the association between using an integrated outpatient-inpatient electronic health record (EHR) and clinician-rated care coordination across delivery sites. Self-administered surveys of primary care clinicians in a large integrated delivery system, collected in 2005 (N=565), 2006 (N=678), and 2008 (N=626) during the staggered implementation of an integrated EHR (2005-2010), including validated questions on team cohesion. Using multivariable regression, we examined the combined effect of EHR use and team cohesion on three dimensions of care coordination across delivery sites: access to timely and complete information, treatment agreement, and responsibility agreement. Among clinicians working in teams with higher cohesion, EHR use was associated with significant improvements in reported access to timely and complete information (53.5 percent with EHR vs. 37.6 percent without integrated-EHR), agreement on treatment goals (64.3 percent vs. 50.6 percent), and agreement on responsibilities (63.9 percent vs. 55.2 percent, all p<.05). We found no statistically significant association between use of the integrated-EHR and reported care coordination in less cohesive teams. The association between EHR use and reported care coordination varied by level of team cohesion. EHRs may not improve care coordination in less cohesive teams. © Health Research and Educational Trust.

Tuning the chromaticity of the emission color of the copolymers containing Eu(III), Tb(III), Be(II) ions based on colorimetric principle

NASA Astrophysics Data System (ADS)

Zhang, Aiqin; Yang, Yamin; Zhai, Guangmei; Jia, Husheng; Xu, Bingshe

2016-02-01

In this work, a method of tuning the chromaticity of the emission color of the copolymers containing Eu(III), Tb(III), Be(II) ions based on colorimetric principle was proposed. The technological route from coordination to copolymerization was employed to obtain the white light macromolecular phosphor. The three primary color monomers have been synthesized and their Commission Internationale de L'Eclairage (CIE) coordinates are respectively (0.540, 0.314), (0.231, 0.463), and (0.161, 0.054). The molar feed ratios of the three primary color monomers were calculated from the CIE coordinates based on colorimetric principle. Serial copolymers have been synthesized by free radical copolymerization of the three primary color monomers and methyl methacrylate. The quantum efficiency of the copolymers was higher than that of the complex monomers. The complexes were directly boned to the polymer chain, in which the energy transfer was reduced significantly compared to the doped-polymers. The experimental values of copolymers' CIE coordinates were located in the white light region in good agreement with theoretical values. The results indicate that the chromaticity of the emission color of the copolymers containing Eu(III), Tb(III), Be(II) ions could be tuned by theoretical calculation based on colorimetric principle.

Specialty-care access for community health clinic patients: processes and barriers.

PubMed

Ezeonwu, Mabel C

2018-01-01

Community health clinics/centers (CHCs) comprise the US's core health-safety net and provide primary care to anyone who walks through their doors. However, access to specialty care for CHC patients is a big challenge. In this descriptive qualitative study, semistructured interviews of 37 referral coordinators of CHCs were used to describe their perspectives on processes and barriers to patients' access to specialty care. Analysis of data was done using content analysis. The process of coordinating care referrals for CHC patients is complex and begins with a provider's order for consultation and ends when the referring provider receives the specialist's note. Poverty, specialist and referral coordinator shortages, lack of insurance, insurance acceptability by providers, transport and clinic-location factors, lack of clinic-hospital affiliations, and poor communication between primary and specialty providers constitute critical barriers to specialty-care access for patients. Understanding the complexities of specialty-care coordination processes and access helps determine the need for comprehensive and uninterrupted access to quality health care for vulnerable populations. Guaranteed access to primary care at CHCs has not translated into improved access to specialty care. It is critical that effective policies be pursued to address the barriers and minimize interruptions in care, and to ensure continuity of care for all patients needing specialty care.

Measuring the Attainment of Primary Care.

ERIC Educational Resources Information Center

Starfield, Barbara

1979-01-01

The definition of primary care is developed and a way is suggested to measure whether it is being achieved. Evaluative questions are identified that can determine whether a system of care is oriented toward primary care. They include assessing first-contact care, coordination of care, comprehensiveness, and longitudinality. (LBH)

Care Coordination and Transitions of Care.

PubMed

Choi, Youngjee

2017-11-01

Care coordination and effective transitions of care are essential for high-quality care in cancer survivors. Aspects of care that require coordination include cancer surveillance, managing the effects of cancer and its treatment, and preventive care, including screening for new cancers, with the clinician responsible for each aspect of care clearly defined. There are many barriers to transitioning and coordinating care across cancer specialists and primary care physicians; possible solutions include survivorship care plans and certain care models. Improving these areas, along with survivorship care training and education, may lead to more effective care coordination and transitions in the future. Copyright © 2017 Elsevier Inc. All rights reserved.

Personal Characteristics and Experience of Primary Care Predicting Frequent Use of Emergency Department: A Prospective Cohort Study.

PubMed

Hudon, Catherine; Sanche, Steven; Haggerty, Jeannie L

2016-01-01

A small number of patients frequently using the emergency department (ED) account for a disproportionate amount of the total ED workload and are considered using this service inappropriately. The aim of this study was to identify prospectively personal characteristics and experience of organizational and relational dimensions of primary care that predict frequent use of ED. This study was conducted among parallel cohorts of the general population and primary care patients (N = 1,769). The measures were at baseline (T1), 12 (T2) and 24 months (T3): self-administered questionnaire on current health, health behaviours and primary care experience in the previous year. Use of medical services was confirmed using administrative databases. Mixed effect logistic regression modeling identified characteristics predicting frequent ED utilization. A higher likelihood of frequent ED utilization was predicted by lower socioeconomic status, higher disease burden, lower perceived organizational accessibility, higher number of reported healthcare coordination problems and not having a complete annual check-up, above and beyond adjustment for all independent variables. Personal characteristics such as low socioeconomic status and high disease burden as well as experience of organizational dimensions of primary care such as low accessibility, high healthcare coordination problems and low comprehensiveness of care are prospectively associated with frequent ED utilization. Interventions developed to prevent inappropriate ED visits, such as case management for example, should tailor low socioeconomic status and patients with high disease burden and should aim to improve experience of primary care regarding accessibility, coordination and comprehensiveness.

42 CFR 425.708 - Beneficiaries may decline data sharing.

Code of Federal Regulations, 2012 CFR

2012-10-01

... beneficiary for purposes of its care coordination and quality improvement work, and give the beneficiary... to decline data sharing as part of their first primary care service visit with an ACO participant... beneficiaries that have a primary care service office visit with an ACO participant who provides primary care...

42 CFR 425.708 - Beneficiaries may decline data sharing.

Code of Federal Regulations, 2014 CFR

2014-10-01

... beneficiary for purposes of its care coordination and quality improvement work, and give the beneficiary... to decline data sharing as part of their first primary care service visit with an ACO participant... beneficiaries that have a primary care service office visit with an ACO participant who provides primary care...

42 CFR 425.708 - Beneficiaries may decline data sharing.

Code of Federal Regulations, 2013 CFR

2013-10-01

... beneficiary for purposes of its care coordination and quality improvement work, and give the beneficiary... to decline data sharing as part of their first primary care service visit with an ACO participant... beneficiaries that have a primary care service office visit with an ACO participant who provides primary care...

75 FR 61157 - Statement of Organization, Functions and Delegations of Authority

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-04

... coordinates personnel activities for BPHC; (3) provides organization and management analysis, coordinating the... Organization, Functions and Delegations of Authority This notice amends Part R of the Statement of Organization... Primary Health Care (RC). Specifically, this notice (1) Creates the Office of Administrative Management...

Coordination and collaboration to document the global cotton germplasm resources

USDA-ARS?s Scientific Manuscript database

Coordinated efforts to collect and maintain cotton genetic resources have increased over the last 100 years to insure the worldwide economic value of cotton fiber and cotton byproducts. The classified genetic resources of cotton are extensive and include five tetraploid species in the primary gene ...

Primary health care and the coordination of care in health regions: managers' and users' perspective.

PubMed

Bousquat, Aylene; Giovanella, Ligia; Campos, Estela Márcia Saraiva; Almeida, Patty Fidelis de; Martins, Cleide Lavieri; Mota, Paulo Henrique Dos Santos; Mendonça, Maria Helena Magalhães de; Medina, Maria Guadalupe; Viana, Ana Luiza d'Ávila; Fausto, Márcia Cristina Rodrigues; Paula, Daniel Baffini de

2017-04-01

This paper aims to analyze the healthcare coordination by Primary Health Care (PHC), with the backdrop of building a Health Care Network (RAS) in a region in the state of São Paulo, Brazil. We conducted a case study with qualitative and quantitative approaches, proceeding to the triangulation of data between the perception of managers and experience of users. We drew analysis realms and variables from the three pillars of healthcare coordination - informational, clinical and administrative/organizational. Stroke was the tracer event chosen and therapeutic itineraries were conducted with users and questionnaires applied to the managers. The central feature of the construction of the Health Care Network in the studied area is the prominence of a philanthropic organization. The results suggest fragility of PHC in healthcare coordination in all analyzed realms. Furthermore, we identified a public-private mix, in addition to services contracted from the Unified Health System (SUS), with out-of-pocket payments for specialist consultation, tests and rehabilitation. Much in the same way that there is no RAS without a robust PHC capable of coordinating care, PHC is unable to play its role without a solid regional arrangement and a virtuous articulation between the three federative levels.

Improvement of Coordination in the Multi-National Military Coordination Center of the Nepal Army in Respond to Disasters

DTIC Science & Technology

2017-06-09

primary question. This thesis has used the case study research methodology with Capability-Based Assessment (CBA) approach. My engagement in this...protected by more restrictions in their home countries, in which case further publication or sale of copyrighted images is not permissible...effective coordinating mechanism. The research follows the case study method utilizing the Capability Based Analysis (CBA) approach to scrutinize the

Optimizing clinical and organizational practice in cancer survivor transitions between specialized oncology and primary care teams: a realist evaluation of multiple case studies.

PubMed

Tremblay, Dominique; Prady, Catherine; Bilodeau, Karine; Touati, Nassera; Chouinard, Maud-Christine; Fortin, Martin; Gaboury, Isabelle; Rodrigue, Jean; L'Italien, Marie-France

2017-12-16

Cancer is now viewed as a chronic disease, presenting challenges to follow-up and survivorship care. Models to shift from haphazard, suboptimal and fragmented episodes of care to an integrated cancer care continuum must be developed, tested and implemented. Numerous studies demonstrate improved care when follow-up is assured by both oncology and primary care providers rather than either group alone. However, there is little data on the roles assumed by specialized oncology teams and primary care providers and the extent to which they work together. This study aims to develop, pilot test and measure outcomes of an innovative risk-based coordinated cancer care model for patients transitioning from specialized oncology teams to primary care providers. This multiple case study using a sequential mixed-methods design rests on a theory-driven realist evaluation approach to understand how transitions might be improved. The cases are two health regions in Quebec, Canada, defined by their geographic territory. Each case includes a Cancer Centre and three Family Medicine Groups selected based on differences in their determining characteristics. Qualitative data will be collected from document review (scientific journal, grey literature, local documentation), semi-directed interviews with key informants, and observation of care coordination practices. Qualitative data will be supplemented with a survey to measure the outcome of the coordinated model among providers (scope of practice, collaboration, relational coordination, leadership) and patients diagnosed with breast, colorectal or prostate cancer (access to care, patient-centredness, communication, self-care, survivorship profile, quality of life). Results from descriptive and regression analyses will be triangulated with thematic analysis of qualitative data. Qualitative, quantitative, and mixed methods data will be interpreted within and across cases in order to identify context-mechanism associations that explain outcomes. The study will provide empirical data on a risk-based coordinated model of cancer care to guide actions at different levels in the health system. This in-depth multiple case study using a realist approach considers both the need for context-specific intervention research and the imperative to address research gaps regarding coordinated models of cancer care.

Applications of laser ranging and VLBI observations for selenodetic control

NASA Technical Reports Server (NTRS)

Fajemirokun, F. A.

1971-01-01

The observation equations necessary to utilize lunar laser ranging and very long baseline interferometry measurements were developed for the establishment of a primary control network on the moon. The network consists of coordinates of moon points in the selenodetic Cartesian coordinate system, which is fixed to the lunar body, oriented along the three principal axes of inertia of the moon, and centered at the lunar center of mass. The observation equations derived are based on a general model in which the unknown parameters included: the selenodetic Cartesian coordinates, the geocentric coordinates of earth stations, parameters of the orientation of the selenodetic coordinate system with respect to a fixed celestial system, the parameters of the orientation of the average terrestrial coordinate system with respect to a fixed celestial coordinate system, and the geocentric coordinates of the center of mass of the moon, given by a lunar ephemeris.

Resources for Linkage of Primary Health Care and Substance Abuse Services.

ERIC Educational Resources Information Center

Edmunds, Margo

1993-01-01

Contends that substance abusing clients benefit from comprehensive and coordinated approach to their medical and psychosocial problems. Suggests range of strategies that have been used to enhance communication among practitioners and agencies and organizations with whom they interact. Describes strategies related to coordination of services;…

Rhode Island State Assessment Program District and School Testing Coordinators Handbook: K-1 Assessment Program

ERIC Educational Resources Information Center

Rhode Island Department of Elementary and Secondary Education, 2007

2007-01-01

This handbook will assist principals and school testing coordinators in implementing the spring 2007 administration of the Developmental Reading Assessment (DRA). Information regarding administration timeline, reporting, process, online tools and contact personnel is discussed. Contents include: (1) Scheduling; (2) Identify Primary Test…

Coordinate metrology of a primary surface composite panel from the Large Millimeter Telescope

NASA Astrophysics Data System (ADS)

Gale, David M.; Lucero Álvarez, Maribel; Cabrera Cuevas, Lizeth; Leon-Huerta, Andrea; Arizmendi Reyes, Edgar; Icasio Hernández, Octavio; Castro Santos, David; Hernández Ríos, Emilio; Tecuapetla Sosa, Esteban; Tzile Torres, Carlos; Viliesid Alonso, Miguel

2016-07-01

The Large Millimeter Telescope (LMT) is a single-dish fully-steerable radio telescope presently operating with a 32.5 m parabolic primary reflector, in the process of extension to 50 m. The project is managed by the Instituto Nacional de Astrofísica, Óptica y Electrónica (INAOE) in México, and the University of Massachusetts Amherst, USA. A laminated surface panel from the LMT primary reflector has been subjected to a surface measurement assay at Mexico's National Metrology Center (CENAM). Data obtained using a coordinate measuring machine and laser tracker owned by CENAM is compared with measurements using an identical model laser tracker and the photogrammetry technique, the latter systems owned and operated by the LMT. All measurements were performed within the controlled metrology environment at CENAM. The measurement exercise is intended to prepare the groundwork for converting this spare surface panel into a calibrated work-piece. The establishment of a calibrated work-piece provides quality assurance for metrology through measurement traceability. It also simplifies the evaluation of measurement uncertainty for coordinate metrology procedures used by the LMT project during reflector surface qualification.

Method and system for assigning a confidence metric for automated determination of optic disc location

DOEpatents

Karnowski, Thomas P [Knoxville, TN; Tobin, Jr., Kenneth W.; Muthusamy Govindasamy, Vijaya Priya [Knoxville, TN; Chaum, Edward [Memphis, TN

2012-07-10

A method for assigning a confidence metric for automated determination of optic disc location that includes analyzing a retinal image and determining at least two sets of coordinates locating an optic disc in the retinal image. The sets of coordinates can be determined using first and second image analysis techniques that are different from one another. An accuracy parameter can be calculated and compared to a primary risk cut-off value. A high confidence level can be assigned to the retinal image if the accuracy parameter is less than the primary risk cut-off value and a low confidence level can be assigned to the retinal image if the accuracy parameter is greater than the primary risk cut-off value. The primary risk cut-off value being selected to represent an acceptable risk of misdiagnosis of a disease having retinal manifestations by the automated technique.

Unlocking information for coordination of care in Australia: a qualitative study of information continuity in four primary health care models

PubMed Central

2013-01-01

Background Coordination of care is considered a key component of patient-centered health care systems, but is rarely defined or operationalised in health care policy. Continuity, an aspect of coordination, is the patient’s experience of care over time, and is often described in terms of three dimensions: information, relational and management continuity. With the current health policy focus on both the use of information technology and care coordination, this study aimed to 1) explore how information continuity supports coordination and 2) investigate conditions required to support information continuity. Methods Four diverse Australian primary health care initiatives were purposively selected for inclusion in the study. Each has improved coordination as an aim or fundamental principle. Each organization was asked to identify practitioners, managers and decision makers who could provide insight into the use of information for care coordination to participate in the study. Using in-depth semi-structured interviews, we explored four questions covering the scope and use of information, the influence of governance, data ownership and confidentiality and the influence of financial incentives and quality improvement on information continuity and coordination. Data were thematically analyzed using NVivo 8. Results The overall picture that emerged across all four cases was that whilst accessibility and continuity of information underpin effective care, they are not sufficient for coordination of care for complex conditions. Shared information reduced unnecessary repetition and provided health professionals with the opportunity to access records of care from other providers, but participants described their role in coordination in terms of the active involvement of a person in care rather than the passive availability of information. Complex issues regarding data ownership and confidentiality often hampered information sharing. Successful coordination in each case was associated with responsiveness to local rather than system level factors. Conclusions The availability of information is not sufficient to ensure continuity for the patient or coordination from the systems perspective. Policy directed at information continuity must give consideration to the broader ‘fit’ with management and relational continuity and provide a broad base that allows for local responsiveness in order for coordination of care to be achieved. PMID:23497291

Unlocking information for coordination of care in Australia: a qualitative study of information continuity in four primary health care models.

PubMed

Banfield, Michelle; Gardner, Karen; McRae, Ian; Gillespie, James; Wells, Robert; Yen, Laurann

2013-03-13

Coordination of care is considered a key component of patient-centered health care systems, but is rarely defined or operationalised in health care policy. Continuity, an aspect of coordination, is the patient's experience of care over time, and is often described in terms of three dimensions: information, relational and management continuity. With the current health policy focus on both the use of information technology and care coordination, this study aimed to 1) explore how information continuity supports coordination and 2) investigate conditions required to support information continuity. Four diverse Australian primary health care initiatives were purposively selected for inclusion in the study. Each has improved coordination as an aim or fundamental principle. Each organization was asked to identify practitioners, managers and decision makers who could provide insight into the use of information for care coordination to participate in the study. Using in-depth semi-structured interviews, we explored four questions covering the scope and use of information, the influence of governance, data ownership and confidentiality and the influence of financial incentives and quality improvement on information continuity and coordination. Data were thematically analyzed using NVivo 8. The overall picture that emerged across all four cases was that whilst accessibility and continuity of information underpin effective care, they are not sufficient for coordination of care for complex conditions. Shared information reduced unnecessary repetition and provided health professionals with the opportunity to access records of care from other providers, but participants described their role in coordination in terms of the active involvement of a person in care rather than the passive availability of information. Complex issues regarding data ownership and confidentiality often hampered information sharing. Successful coordination in each case was associated with responsiveness to local rather than system level factors. The availability of information is not sufficient to ensure continuity for the patient or coordination from the systems perspective. Policy directed at information continuity must give consideration to the broader 'fit' with management and relational continuity and provide a broad base that allows for local responsiveness in order for coordination of care to be achieved.

The strength of primary care in Europe: an international comparative study.

PubMed

Kringos, Dionne; Boerma, Wienke; Bourgueil, Yann; Cartier, Thomas; Dedeu, Toni; Hasvold, Toralf; Hutchinson, Allen; Lember, Margus; Oleszczyk, Marek; Rotar Pavlic, Danica; Svab, Igor; Tedeschi, Paolo; Wilm, Stefan; Wilson, Andrew; Windak, Adam; Van der Zee, Jouke; Groenewegen, Peter

2013-11-01

A suitable definition of primary care to capture the variety of prevailing international organisation and service-delivery models is lacking. Evaluation of strength of primary care in Europe. International comparative cross-sectional study performed in 2009-2010, involving 27 EU member states, plus Iceland, Norway, Switzerland, and Turkey. Outcome measures covered three dimensions of primary care structure: primary care governance, economic conditions of primary care, and primary care workforce development; and four dimensions of primary care service-delivery process: accessibility, comprehensiveness, continuity, and coordination of primary care. The primary care dimensions were operationalised by a total of 77 indicators for which data were collected in 31 countries. Data sources included national and international literature, governmental publications, statistical databases, and experts' consultations. Countries with relatively strong primary care are Belgium, Denmark, Estonia, Finland, Lithuania, the Netherlands, Portugal, Slovenia, Spain, and the UK. Countries either have many primary care policies and regulations in place, combined with good financial coverage and resources, and adequate primary care workforce conditions, or have consistently only few of these primary care structures in place. There is no correlation between the access, continuity, coordination, and comprehensiveness of primary care of countries. Variation is shown in the strength of primary care across Europe, indicating a discrepancy in the responsibility given to primary care in national and international policy initiatives and the needed investments in primary care to solve, for example, future shortages of workforce. Countries are consistent in their primary care focus on all important structure dimensions. Countries need to improve their primary care information infrastructure to facilitate primary care performance management.

Coordinating Mental Health Care across Primary Care and Schools: ADHD as a Case Example

ERIC Educational Resources Information Center

Power, Thomas J.; Blum, Nathan J.; Guevara, James P.; Jones, Heather A.; Leslie, Laurel K.

2013-01-01

Although primary care practices and schools are major venues for the delivery of mental health services to children, these systems are disconnected, contributing to fragmentation in service delivery. This paper describes barriers to collaboration across the primary care and school systems, including administrative and fiscal pressures, conceptual…

Pediatric Primary Care as a Component of Systems of Care

ERIC Educational Resources Information Center

Brown, Jonathan D.

2010-01-01

Systems of care should be defined in a manner that includes primary care. The current definition of systems of care shares several attributes with the definition of primary care: both are defined as community-based services that are accessible, accountable, comprehensive, coordinated, culturally competent, and family focused. However, systems of…

Developing a research agenda for patient safety in primary care. Background, aims and output of the LINNEAUS collaboration on patient safety in primary care.

PubMed

Esmail, Aneez; Valderas, Jose M; Verstappen, Wim; Godycki-Cwirko, Maciek; Wensing, Michel

2015-09-01

This paper is an introduction to a supplement to The European Journal of General Practice, bringing together a body of research focusing on the issue of patient safety in relation to primary care. The supplement represents the outputs of the LINNEAUS collaboration on patient safety in primary care, which was a four-year (2009-2013) coordination and support action funded under the Framework 7 programme by the European Union. Being a coordination and support action, its aim was not to undertake new research, but to build capacity through engaging primary care researchers and practitioners in identifying some of the key challenges in this area and developing consensus statements, which will be an essential part in developing a future research agenda. This introductory article describes the aims of the LINNEAUS collaboration, provides a brief summary of the reasons to focus on patient safety in primary care, the epidemiological and policy considerations, and an introduction to the papers included in the supplement.

Developing a research agenda for patient safety in primary care. Background, aims and output of the LINNEAUS collaboration on patient safety in primary care

PubMed Central

Esmail, Aneez; Valderas, Jose M.; Verstappen, Wim; Godycki-Cwirko, Maciek; Wensing, Michel

2015-01-01

ABSTRACT This paper is an introduction to a supplement to The European Journal of General Practice, bringing together a body of research focusing on the issue of patient safety in relation to primary care. The supplement represents the outputs of the LINNEAUS collaboration on patient safety in primary care, which was a four-year (2009–2013) coordination and support action funded under the Framework 7 programme by the European Union. Being a coordination and support action, its aim was not to undertake new research, but to build capacity through engaging primary care researchers and practitioners in identifying some of the key challenges in this area and developing consensus statements, which will be an essential part in developing a future research agenda. This introductory article describes the aims of the LINNEAUS collaboration, provides a brief summary of the reasons to focus on patient safety in primary care, the epidemiological and policy considerations, and an introduction to the papers included in the supplement. PMID:26339828

Setting standards at the forefront of delivery system reform: aligning care coordination quality measures for multiple chronic conditions.

PubMed

DuGoff, Eva H; Dy, Sydney; Giovannetti, Erin R; Leff, Bruce; Boyd, Cynthia M

2013-01-01

The primary study objective is to assess how three major health reform care coordination initiatives (Accountable Care Organizations, Independence at Home, and Community-Based Care Transitions) measure concepts critical to care coordination for people with multiple chronic conditions. We find that there are major differences in quality measurement across these three large and politically important programs. Quality measures currently used or proposed for these new health reform-related programs addressing care coordination primarily capture continuity of care. Other key areas of care coordination, such as care transitions, patient-centeredness, and cross-cutting care across multiple conditions are infrequently addressed. The lack of a comprehensive and consistent measure set for care coordination will pose challenges for healthcare providers and policy makers who seek, respectively, to provide and reward well-coordinated care. In addition, this heterogeneity in measuring care coordination quality will generate new information, but will inhibit comparisons between these care coordination programs. © 2013 National Association for Healthcare Quality.

Setting Standards at the Forefront of Delivery System Reform: Aligning Care Coordination Quality Measures for Multiple Chronic Conditions

PubMed Central

DuGoff, Eva H.; Dy, Sydney; Giovannetti, Erin R.; Leff, Bruce; Boyd, Cynthia M.

2015-01-01

The primary study objective is to assess how three major health reform care coordination initiatives (Accountable Care Organizations, Independence at Home, and Community-based Care Transitions) measure concepts critical to care coordination for people with multiple chronic conditions. We find that there are major differences in quality measurement across these three large and politically important programs. Quality measures currently used or proposed for these new health reform-related programs addressing care coordination primarily capture continuity of care. Other key areas of care coordination, such as care transitions, patient-centeredness, and cross-cutting care across multiple conditions are infrequently addressed. The lack of a comprehensive and consistent measure set for care coordination will pose challenges for health care providers and policymakers who seek, respectively, to provide and reward well-coordinated care. In addition, this heterogeneity in measuring care coordination quality will generate new information, but will inhibit comparisons between these care coordination programs. PMID:24004040

Specialty-care access for community health clinic patients: processes and barriers

PubMed Central

Ezeonwu, Mabel C

2018-01-01

Introduction Community health clinics/centers (CHCs) comprise the US’s core health-safety net and provide primary care to anyone who walks through their doors. However, access to specialty care for CHC patients is a big challenge. Materials and methods In this descriptive qualitative study, semistructured interviews of 37 referral coordinators of CHCs were used to describe their perspectives on processes and barriers to patients’ access to specialty care. Analysis of data was done using content analysis. Results The process of coordinating care referrals for CHC patients is complex and begins with a provider’s order for consultation and ends when the referring provider receives the specialist’s note. Poverty, specialist and referral coordinator shortages, lack of insurance, insurance acceptability by providers, transport and clinic-location factors, lack of clinic–hospital affiliations, and poor communication between primary and specialty providers constitute critical barriers to specialty-care access for patients. Conclusion Understanding the complexities of specialty-care coordination processes and access helps determine the need for comprehensive and uninterrupted access to quality health care for vulnerable populations. Guaranteed access to primary care at CHCs has not translated into improved access to specialty care. It is critical that effective policies be pursued to address the barriers and minimize interruptions in care, and to ensure continuity of care for all patients needing specialty care. PMID:29503559

Assessment of the coordination of integrated health service delivery networks by the primary health care: COPAS questionnaire validation in the Brazilian context.

PubMed

Rodrigues, Ludmila Barbosa Bandeira; Dos Santos, Claudia Benedita; Goyatá, Sueli Leiko Takamatsu; Popolin, Marcela Paschoal; Yamamura, Mellina; Deon, Keila Christiane; Lapão, Luis Miguel Veles; Santos Neto, Marcelino; Uchoa, Severina Alice da Costa; Arcêncio, Ricardo Alexandre

2015-07-22

Health systems organized as networks and coordinated by the Primary Health Care (PHC) may contribute to the improvement of clinical care, sanitary conditions, satisfaction of patients and reduction of local budget expenditures. The aim of this study was to adapt and validate a questionnaire - COPAS - to assess the coordination of Integrated Health Service Delivery Networks by the Primary Health Care. A cross sectional approach was used. The population was pooled from Family Health Strategy healthcare professionals, of the Alfenas region (Minas Gerais, Brazil). Data collection was performed from August to October 2013. The results were checked for the presence of floor and ceiling effects and the internal consistency measured through Cronbach alpha. Construct validity was verified through convergent and discriminant values following Multitrait-Multimethod (MTMM) analysis. Floor and ceiling effects were absent. The internal consistency of the instrument was satisfactory; as was the convergent validity, with a few correlations lower then 0.30. The discriminant validity values of the majority of items, with respect to their own dimension, were found to be higher or significantly higher than their correlations with the dimensions to which they did not belong. The results showed that the COPAS instrument has satisfactory initial psychometric properties and may be used by healthcare managers and workers to assess the PHC coordination performance within the Integrated Health Service Delivery Network.

Doctors' experience of coordination across care levels and associated factors. A cross-sectional study in public healthcare networks of six Latin American countries.

PubMed

Vázquez, María-Luisa; Vargas, Ingrid; Garcia-Subirats, Irene; Unger, Jean-Pierre; De Paepe, Pierre; Mogollón-Pérez, Amparo Susana; Samico, Isabella; Eguiguren, Pamela; Cisneros, Angelica-Ivonne; Huerta, Adriana; Muruaga, María-Cecilia; Bertolotto, Fernando

2017-06-01

Improving coordination between primary care (PC) and secondary care (SC) has become a policy priority in recent years for many Latin American public health systems looking to reinforce a healthcare model based on PC. However, despite being a longstanding concern, it has scarcely been analyzed in this region. This paper analyses the level of clinical coordination between PC and SC experienced by doctors and explores influencing factors in public healthcare networks of Argentina, Brazil, Chile, Colombia, Mexico and Uruguay. A cross-sectional study was carried out based on a survey of doctors working in the study networks (348 doctors per country). The COORDENA questionnaire was applied to measure their experiences of clinical management and information coordination, and their related factors. Descriptive analyses were conducted and a multivariate logistic regression model was generated to assess the relationship between general perception of care coordination and associated factors. With some differences between countries, doctors generally reported limited care coordination, mainly in the transfer of information and communication for the follow-up of patients and access to SC for referred patients, especially in the case of PC doctors and, to a lesser degree, inappropriate clinical referrals and disagreement over treatments, in the case of SC doctors. Factors associated with a better general perception of coordination were: being a SC doctor, considering that there is enough time for coordination within consultation hours, job and salary satisfaction, identifying the PC doctor as the coordinator of patient care across levels, knowing the doctors of the other care level and trusting in their clinical skills. These results provide evidence of problems in the implementation of a primary care-based model that require changes in aspects of employment, organization and interaction between doctors, all key factors for coordination. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Evaluating the potential for primary care to serve as a mental health home for people with schizophrenia.

PubMed

Grove, Lexie R; Olesiuk, William J; Ellis, Alan R; Lichstein, Jesse C; DuBard, C Annette; Farley, Joel F; Jackson, Carlos T; Beadles, Christopher A; Morrissey, Joseph P; Domino, Marisa Elena

2017-07-01

Primary care-based medical homes could improve the coordination of mental health care for individuals with schizophrenia and comorbid chronic conditions. The objective of this paper is to examine whether persons with schizophrenia and comorbid chronic conditions engage in primary care regularly, such that primary care settings have the potential to serve as a mental health home. We examined the annual primary care and specialty mental health service utilization of adult North Carolina Medicaid enrollees with schizophrenia and at least one comorbid chronic condition who were in a medical home during 2007-2010. Using a fixed-effects regression approach, we also assessed the effect of medical home enrollment on utilization of primary care and specialty mental health care and medication adherence. A substantial majority (78.5%) of person-years had at least one primary care visit, and 17.9% had at least one primary care visit but no specialty mental health services use. Medical home enrollment was associated with increased use of primary care and specialty mental health care, as well as increased medication adherence. Medical home enrollees with schizophrenia and comorbid chronic conditions exhibited significant engagement in primary care, suggesting that primary-care-based medical homes could serve a care coordination function for persons with schizophrenia. Copyright © 2017 Elsevier Inc. All rights reserved.

Predicting Use of Nurse Care Coordination by Older Adults With Chronic Conditions.

PubMed

Vanderboom, Catherine E; Holland, Diane E; Mandrekar, Jay; Lohse, Christine M; Witwer, Stephanie G; Hunt, Vicki L

2017-07-01

To be effective, nurse care coordination must be targeted at individuals who will use the service. The purpose of this study was to identify variables that predicted use of care coordination by primary care patients. Data on the potential predictor variables were obtained from patient interviews, the electronic health record, and an administrative database of 178 adults eligible for care coordination. Use of care coordination was obtained from an administrative database. A multivariable logistic regression model was developed using a bootstrap sampling approach. Variables predicting use of care coordination were dependence in both activities of daily living (ADL) and instrumental activities of daily living (IADL; odds ratio [OR] = 5.30, p = .002), independent for ADL but dependent for IADL (OR = 2.68, p = .01), and number of prescription medications (OR = 1.12, p = .002). Consideration of these variables may improve identification of patients to target for care coordination.

The Standards Agenda: Reflections of a Special Educational Needs Co-ordinator

ERIC Educational Resources Information Center

Glazzard, Jonathan

2014-01-01

This study is a life history account of Bev, a special educational needs co-ordinator who works in a primary school in England. The research examines how, within Bev's experiences, the discourses of integration and inclusion have affected learners with special educational needs. Additionally, the study examines the impact of the…

75 FR 42376 - Proposed Information Collection; Comment Request; NTIA/FCC Web-based Frequency Coordination System

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-21

... Information Collection; Comment Request; NTIA/FCC Web- based Frequency Coordination System AGENCY: National.... Abstract The National Telecommunications and Information Administration (NTIA) hosts a Web-based system...) bands that are shared on a co-primary basis by federal and non-federal users. The Web-based system...

78 FR 49480 - Proposed Information Collection; Comment Request; NTIA/FCC Web-based Frequency Coordination System

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-14

... Information Collection; Comment Request; NTIA/FCC Web- based Frequency Coordination System AGENCY: National... INFORMATION: I. Abstract The National Telecommunications and Information Administration (NTIA) hosts a web... (RF) bands that are shared on a co-primary basis by federal and non-federal users. The web-based...

The Role of Communication in Library Management. Occasional Paper No. 34.

ERIC Educational Resources Information Center

Mwenegoha, Hamza A.

This paper defines and discusses the nature of management; outlines the primary management functions and activities, emphasizing the importance of communication and coordination to successful management; and examines the place of communication as a management function in the library setting. After a discussion of the key role of coordination in…

The Community Education Coordinator: Sources of Job Satisfaction and Dissatisfaction.

ERIC Educational Resources Information Center

Sheppard, Bunny G.

The determination of those factors of motivation and hygiene which led to job satisfaction/dissatisfaction of forty-five randomly selected community education coordinators in six mid-Atlantic states was the primary purpose of this interview-oriented research study. A second purpose was to examine the relationship between age, gender, marital…

34 CFR 692.100 - What requirements must a State meet to receive an allotment under this program?

Code of Federal Regulations, 2014 CFR

2014-07-01

... plan for using the Federal funds allotted under this subpart and the non-Federal matching funds; and... applicable, other contributing partners. (b) Serve as the primary administrative unit for the partnership; (c) Provide or coordinate non-Federal share funds, and coordinate activities among partners; (d) Encourage...

34 CFR 692.100 - What requirements must a State meet to receive an allotment under this program?

Code of Federal Regulations, 2011 CFR

2011-07-01

... plan for using the Federal funds allotted under this subpart and the non-Federal matching funds; and... applicable, other contributing partners. (b) Serve as the primary administrative unit for the partnership; (c) Provide or coordinate non-Federal share funds, and coordinate activities among partners; (d) Encourage...

34 CFR 692.100 - What requirements must a State meet to receive an allotment under this program?

Code of Federal Regulations, 2010 CFR

2010-07-01

... Federal funds allotted under this subpart and the non-Federal matching funds; and (ii) The methods by..., other contributing partners. (b) Serve as the primary administrative unit for the partnership; (c) Provide or coordinate non-Federal share funds, and coordinate activities among partners; (d) Encourage...

34 CFR 692.100 - What requirements must a State meet to receive an allotment under this program?

Code of Federal Regulations, 2012 CFR

2012-07-01

... plan for using the Federal funds allotted under this subpart and the non-Federal matching funds; and... applicable, other contributing partners. (b) Serve as the primary administrative unit for the partnership; (c) Provide or coordinate non-Federal share funds, and coordinate activities among partners; (d) Encourage...

34 CFR 692.100 - What requirements must a State meet to receive an allotment under this program?

Code of Federal Regulations, 2013 CFR

2013-07-01

... plan for using the Federal funds allotted under this subpart and the non-Federal matching funds; and... applicable, other contributing partners. (b) Serve as the primary administrative unit for the partnership; (c) Provide or coordinate non-Federal share funds, and coordinate activities among partners; (d) Encourage...

Wisconsin Card Sorting Test Performance in Children with Developmental Coordination Disorder

ERIC Educational Resources Information Center

Wuang, Yee-Pay; Su, Chwen-Yng; Su, Jui-Hsing

2011-01-01

The primary purpose of this study was to investigate and compare the executive functions measured by the Wisconsin Card Sorting Test (WCST) between children with developmental coordination disorder (DCD) and age-matched normal controls. A second purpose was to examine the relations between executive functions and school functions in DCD children.…

Nurse-led multidisciplinary initiatives to improve outcomes and reduce hospital admissions for older adults: The Care coordination through Emergency Department, Residential Aged Care and Primary Health Collaboration project.

PubMed

Marsden, Elizabeth; Craswell, Alison; Taylor, Andrea; Coates, Kaye; Crilly, Julia; Broadbent, Marc; Glenwright, Amanda; Johnston, Colleen; Wallis, Marianne

2018-04-03

This article describes the Care coordination through Emergency Department, Residential Aged Care and Primary Health Collaboration (CEDRiC) project. CEDRiC is designed to improve the health outcomes for older people with an acute illness. It attempts this via enhanced primary care in residential aged care facilities, focused and streamlined care in the emergency department and enhanced intersectoral communication and referral. Implementing this approach has the potential to decrease inappropriate hospital admissions while improving care for older people in residential aged care and community settings. This article discusses an innovative way of caring for older adults in an ageing population utilising the existing evidence. A formal evaluation is currently underway. © 2018 AJA Inc.

Securing recipiency in workplace meetings: Multimodal practices

PubMed Central

Ford, Cecilia E.; Stickle, Trini

2013-01-01

As multiparty interactions with single courses of coordinated action, workplace meetings place particular interactional demands on participants who are not primary speakers (e.g. not chairs) as they work to initiate turns and to interactively coordinate with displays of recipiency from co-participants. Drawing from a corpus of 26 hours of videotaped workplace meetings in a midsized US city, this article reports on multimodal practices – phonetic, prosodic, and bodily-visual – used for coordinating turn transition and for consolidating recipiency in these specialized speech exchange systems. Practices used by self-selecting non-primary speakers as they secure turns in meetings include displays of close monitoring of current speakers’ emerging turn structure, displays of heightened interest as current turns approach possible completion, and turn initiation practices designed to pursue and, in a fine-tuned manner, coordinate with displays of recipiency on the parts of other participants as well as from reflexively constructed ‘target’ recipients. By attending to bodily-visual action, as well as phonetics and prosody, this study contributes to expanding accounts for turn taking beyond traditional word-based grammar (i.e. lexicon and syntax). PMID:24976789

[The factors that influence the use of clinical protocols according to the opinion of health center coordinators. The Research Group on the Evaluation and Improvement of Clinical Protocols].

PubMed

Saura-Llamas, J; Saturno Hernández, P J; Gaona Ramón, J M; Romero Román, J R; González Barberá, M

1999-11-15

To find the factors that affect the use of clinical protocols in primary care, in the view of primary care team coordinators, and the reasons why they are little followed, and to bring together suggestions for improvement. An opinion study, through a telephone survey. Primary health care. The health centres in Murcia with protocolized activity: 31 at the start of the project. The coordinators and those in charge of nursing, 62 people in all. After a pilot study, a structured telephone survey was carried out, administered by a trained interviewer who posed two open questions: why do you think that the professionals at your centre do not use the existing protocols more often? and: what suggestions would you make to improve the protocols and have them used more? A specialist company did the field-work in June and July 1996. There was a 98% reply rate. To the first question, coordinators thought that low use could be explained by excess demand and lack of time for consultations (33% of all replies), although they also cited other organisational problems in the centre, defects in protocols and lack of training. Those in charge of nursing gave very similar replies, with excess demand (39%) predominating. To the second question, on increasing the use of protocols, coordinators suggested that the protocols needed to be improved (44.8% of replies), and also cited the need for improvements in organisation and on-going training. Very similar answers came from the nursing side, where 43.5% highlighted the need to improve the protocol documents. The coordinators assumed that the clinical protocols were used little and could be improved. In their view the basic reason for their low use is excessive pressure from the patient-load. The key to using them more is improvement in the protocol documents.

Use Root Cause Analysis Teaching Strategy to Train Primary Pre-Service Science Teachers

ERIC Educational Resources Information Center

Lu, Chow-chin; Tsai, Chun-wei; Hong, Jon-chao

2008-01-01

This study examined the Root Cause Analysis (RCA) teaching strategy on pre-service primary science teachers and instinct pre-service teachers to apply RCA teaching strategy to science curriculums. RCA Teaching Strategy is to coordinates 5 Why Method and Fishbone Diagram. The participants included 18 pre-service primary science teachers and the…

Possibility of Identifying the Logical-Mathematical Giftedness with Students of Lower Primary School Grades through Evaluations

ERIC Educational Resources Information Center

Milic, Sanja; Simeunovic, Vlado

2017-01-01

The objective of this work is examination of co-ordinance amongst assessments of logical-mathematical giftedness with young primary school students, made by four groups of evaluators: teachers, parents, coevals and self-evaluators. Teachers of 11 primary schools selected at the area of Republic Srpska were assigned to follow Instructions for…

Instructional Leadership for Quality Learning: An Assessment of the Impact of the Primary School Management Development Project in Botswana

ERIC Educational Resources Information Center

Pansiri, Nkobi Owen

2008-01-01

A descriptive study using questionnaires was conducted in 2004 to assess the effectiveness of instructional leadership displayed by primary school management teams following the implementation of the Primary School Management Project in Botswana. Leadership skills, Coordination of instructional activities, management of curriculum and quality of…

Integrating Behavioral Health and Primary Care: Consulting, Coordinating and Collaborating Among Professionals.

PubMed

Cohen, Deborah J; Davis, Melinda; Balasubramanian, Bijal A; Gunn, Rose; Hall, Jennifer; deGruy, Frank V; Peek, C J; Green, Larry A; Stange, Kurt C; Pallares, Carla; Levy, Sheldon; Pollack, David; Miller, Benjamin F

2015-01-01

This paper sought to describe how clinicians from different backgrounds interact to deliver integrated behavioral and primary health care, and the contextual factors that shape such interactions. This was a comparative case study in which a multidisciplinary team used an immersion-crystallization approach to analyze data from observations of practice operations, interviews with practice members, and implementation diaries. The observed practices were drawn from 2 studies: Advancing Care Together, a demonstration project of 11 practices located in Colorado; and the Integration Workforce Study, consisting of 8 practices located across the United States. Primary care and behavioral health clinicians used 3 interpersonal strategies to work together in integrated settings: consulting, coordinating, and collaborating (3Cs). Consulting occurred when clinicians sought advice, validated care plans, or corroborated perceptions of a patient's needs with another professional. Coordinating involved 2 professionals working in a parallel or in a back-and-forth fashion to achieve a common patient care goal, while delivering care separately. Collaborating involved 2 or more professionals interacting in real time to discuss a patient's presenting symptoms, describe their views on treatment, and jointly develop a care plan. Collaborative behavior emerged when a patient's care or situation was complex or novel. We identified contextual factors shaping use of the 3Cs, including: time to plan patient care, staffing, employing brief therapeutic approaches, proximity of clinical team members, and electronic health record documenting behavior. Primary care and behavioral health clinicians, through their interactions, consult, coordinate, and collaborate with each other to solve patients' problems. Organizations can create integrated care environments that support these collaborations and health professions training programs should equip clinicians to execute all 3Cs routinely in practice. © Copyright 2015 by the American Board of Family Medicine.

A practice-based information system for multi-disciplinary care of chronically ill patients: what information do we need? The Community Care Coordination Network Database Group.

PubMed Central

Moran, W. P.; Messick, C.; Guerette, P.; Anderson, R.; Bradham, D.; Wofford, J. L.; Velez, R.

1994-01-01

Primary care physicians provide longitudinal care for chronically ill individuals in concert with many other community-based disciplines. The care management of these individuals requires data not traditionally collected during the care of well, or acutely ill individuals. These data not only concern the patient, in the form of patient functional status, mental status and affect, but also pertain to the caregiver, home environment, and the formal community health and social service system. The goal of the Community Care Coordination Network is to build a primary care-based information system to share patient data and communicate patient related information among the community-based multi-disciplinary teams. One objective of the Community Care Coordination Network is to create a Community Care Database for chronically ill individuals by identifying those data elements necessary for efficient multi-disciplinary care. PMID:7949995

Three-dimensional Culture of Human Airway Epithelium in Matrigel for Evaluation of Human Rhinovirus C and Bocavirus Infections.

PubMed

Chen, A Xiong; Xie, Guang Cheng; Pan, Dong; DU, Ya Rong; Pang, Li Li; Song, Jing Dong; Duan, Zhao Jun; Hu, Bu Rong

2018-02-01

Newly identified human rhinovirus C (HRV-C) and human bocavirus (HBoV) cannot propagate in vitro in traditional cell culture models; thus obtaining knowledge about these viruses and developing related vaccines are difficult. Therefore, it is necessary to develop a novel platform for the propagation of these types of viruses. A platform for culturing human airway epithelia in a three-dimensional (3D) pattern using Matrigel as scaffold was developed. The features of 3D culture were identified by immunochemical staining and transmission electron microscopy. Nucleic acid levels of HRV-C and HBoV in 3D cells at designated time points were quantitated by real-time polymerase chain reaction (PCR). Levels of cytokines, whose secretion was induced by the viruses, were measured by ELISA. Properties of bronchial-like tissues, such as the expression of biomarkers CK5, ZO-1, and PCK, and the development of cilium-like protuberances indicative of the human respiration tract, were observed in 3D-cultured human airway epithelial (HAE) cultures, but not in monolayer-cultured cells. Nucleic acid levels of HRV-C and HBoV and levels of virus-induced cytokines were also measured using the 3D culture system. Our data provide a preliminary indication that the 3D culture model of primary epithelia using a Matrigel scaffold in vitro can be used to propagate HRV-C and HBoV. Copyright © 2018 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

Cell- and subunit-specific mechanisms of CNG channel ciliary trafficking and localization in C. elegans

PubMed Central

Wojtyniak, Martin; Brear, Andrea G.; O'Halloran, Damien M.; Sengupta, Piali

2013-01-01

Summary Primary cilia are ubiquitous sensory organelles that concentrate transmembrane signaling proteins essential for sensing environmental cues. Mislocalization of crucial ciliary signaling proteins, such as the tetrameric cyclic nucleotide-gated (CNG) channels, can lead to cellular dysfunction and disease. Although several cis- and trans-acting factors required for ciliary protein trafficking and localization have been identified, whether these mechanisms act in a protein- and cell-specific manner is largely unknown. Here, we show that CNG channel subunits can be localized to discrete ciliary compartments in individual sensory neurons in C. elegans, suggesting that channel composition is heterogeneous across the cilium. We demonstrate that ciliary localization of CNG channel subunits is interdependent on different channel subunits in specific cells, and identify sequences required for efficient ciliary targeting and localization of the TAX-2 CNGB and TAX-4 CNGA subunits. Using a candidate gene approach, we show that Inversin, transition zone proteins, intraflagellar transport motors and a MYND-domain protein are required to traffic and/or localize CNG channel subunits in both a cell- and channel subunit-specific manner. We further find that TAX-2 and TAX-4 are relatively immobile in specific sensory cilia subcompartments, suggesting that these proteins undergo minimal turnover in these domains in mature cilia. Our results uncover unexpected diversity in the mechanisms that traffic and localize CNG channel subunits to cilia both within and across cell types, highlighting the essential contribution of this process to cellular functions. PMID:23886944

Quantifying Ciliary Dynamics during Assembly Reveals Step-wise Waveform Maturation in Airway Cells.

PubMed

Oltean, Alina; Schaffer, Andrew J; Bayly, Philip V; Brody, Steven L

2018-05-31

Motile cilia are essential for clearance of particulates and pathogens from airways. For effective transport, ciliary motor proteins and axonemal structures interact to generate the rhythmic, propulsive bending, but the mechanisms that produce a dynamic waveform remain incompletely understood. Biomechanical measures of human cilia motion and their relationships to cilia assembly are needed to illuminate the biophysics of normal cilia function, and to quantify dysfunction in ciliopathies. To these ends, we analyzed cilia motion from high-speed video microscopy of ciliated cells sampled from human lung airways compared to primary-culture cells that undergo ciliogenesis in vitro. Quantitative assessment of waveform parameters showed variations in waveform shape between individual cilia; however, general trends in waveform parameters emerged, associated with progression of cilia length and stage of differentiation. When cilia emerged from cultured cells, beat frequency was initially elevated, then fell and remained stable as cilia lengthened. In contrast, the average bending amplitude and the ability to generate force gradually increased and eventually approached values observed in ex vivo samples. Dynein arm motor proteins DNAH5, DNAH9, DNAH11, and DNAH6 were localized within specific regions of the axoneme in the ex vivo cells; however distinct stages of in vitro waveform development identified by biomechanical features were associated with the progressive movement of dyneins to the appropriate proximal or distal sections of the cilium. These observations suggest that the step-wise variation in waveform development during ciliogenesis is dependent on cilia length and potentially outer dynein arm assembly.

Early photoreceptor outer segment loss and retinoschisis in Cohen syndrome.

PubMed

Uyhazi, Katherine E; Binenbaum, Gil; Carducci, Nicholas; Zackai, Elaine H; Aleman, Tomas S

2018-06-01

To describe early structural and functional retinal changes in a patient with Cohen syndrome. A 13-month-old Caucasian girl of Irish and Spanish ancestry was noted to have micrognathia and laryngomalacia at birth, which prompted a genetic evaluation that revealed biallelic deletions in COH1 (VPS13B) (a maternally inherited 60-kb deletion involving exons 26-32 and a paternally inherited 3.5-kb deletion within exon 17) consistent with Cohen syndrome. She underwent a complete ophthalmic examination, full-field flash electroretinography and retinal imaging with spectral domain optical coherence tomography. Central vision was central, steady, and maintained. There was bilateral myopic astigmatic refractive error. Fundus exam was notable for dark foveolar pigmentation, but no obvious abnormalities of either eye. Spectral domain optical coherence tomography cross sections through the fovea revealed a normal appearing photoreceptor outer nuclear layer but loss of the interdigitation signal between the photoreceptor outer segments and the apical retinal pigment epithelium. Retinoschisis involving the inner nuclear layer of both eyes and possible ganglion cell layer thinning were also noted. There was a detectable electroretinogram with similarly reduced amplitudes of rod- (white, 0.01 cd.s.m -2 ) and cone-mediated (3 cd.s.m -2 , 30 Hz) responses. Photoreceptor outer segment abnormalities and retinoschisis may represent the earliest structural retinal change detected by spectral domain optical coherence tomography in patients with Cohen syndrome, suggesting a complex pathophysiology with primary involvement of the photoreceptor cilium and disorganization of the structural integrity of the inner retina.

Cell- and subunit-specific mechanisms of CNG channel ciliary trafficking and localization in C. elegans.

PubMed

Wojtyniak, Martin; Brear, Andrea G; O'Halloran, Damien M; Sengupta, Piali

2013-10-01

Primary cilia are ubiquitous sensory organelles that concentrate transmembrane signaling proteins essential for sensing environmental cues. Mislocalization of crucial ciliary signaling proteins, such as the tetrameric cyclic nucleotide-gated (CNG) channels, can lead to cellular dysfunction and disease. Although several cis- and trans-acting factors required for ciliary protein trafficking and localization have been identified, whether these mechanisms act in a protein- and cell-specific manner is largely unknown. Here, we show that CNG channel subunits can be localized to discrete ciliary compartments in individual sensory neurons in C. elegans, suggesting that channel composition is heterogeneous across the cilium. We demonstrate that ciliary localization of CNG channel subunits is interdependent on different channel subunits in specific cells, and identify sequences required for efficient ciliary targeting and localization of the TAX-2 CNGB and TAX-4 CNGA subunits. Using a candidate gene approach, we show that Inversin, transition zone proteins, intraflagellar transport motors and a MYND-domain protein are required to traffic and/or localize CNG channel subunits in both a cell- and channel subunit-specific manner. We further find that TAX-2 and TAX-4 are relatively immobile in specific sensory cilia subcompartments, suggesting that these proteins undergo minimal turnover in these domains in mature cilia. Our results uncover unexpected diversity in the mechanisms that traffic and localize CNG channel subunits to cilia both within and across cell types, highlighting the essential contribution of this process to cellular functions.

Attributes of patient-centered primary care associated with the public perception of good healthcare quality in Brazil, Colombia, Mexico and El Salvador.

PubMed

Doubova, Svetlana V; Guanais, Frederico C; Pérez-Cuevas, Ricardo; Canning, David; Macinko, James; Reich, Michael R

2016-09-01

This study evaluated primary care attributes of patient-centered care associated with the public perception of good quality in Brazil, Colombia, Mexico and El Salvador. We conducted a secondary data analysis of a Latin American survey on public perceptions and experiences with healthcare systems. The primary care attributes examined were access, coordination, provider-patient communication, provision of health-related information and emotional support. A double-weighted multiple Poisson regression with robust variance model was performed. The study included between 1500 and 1503 adults in each country. The results identified four significant gaps in the provision of primary care: not all respondents had a regular place of care or a regular primary care doctor (Brazil 35.7%, Colombia 28.4%, Mexico 22% and El Salvador 45.4%). The communication with the primary care clinic was difficult (Brazil 44.2%, Colombia 41.3%, Mexico 45.1% and El Salvador 56.7%). There was a lack of coordination of care (Brazil 78.4%, Colombia 52.3%, Mexico 48% and El Salvador 55.9%). Also, there was a lack of information about healthy diet (Brazil 21.7%, Colombia 32.9%, Mexico 16.9% and El Salvador 20.8%). The public's perception of good quality was variable (Brazil 67%, Colombia 71.1%, Mexico 79.6% and El Salvador 79.5%). The primary care attributes associated with the perception of good quality were a primary care provider 'who knows relevant information about a patient's medical history', 'solves most of the health problems', 'spends enough time with the patient', 'coordinates healthcare' and a 'primary care clinic that is easy to communicate with'. In conclusion, the public has a positive perception of the quality of primary care, although it has unfulfilled expectations; further efforts are necessary to improve the provision of patient-centered primary care services in these four Latin American countries. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Associations of family characteristics with perceptions of care among parents of children with autism.

PubMed

Sobotka, S A; Francis, A; Vander Ploeg Booth, K

2016-01-01

Although autism spectrum disorder (ASD) is an increasingly common chronic disability, primary care provider (PCPs) report deficits in providing primary care for children with ASD, and parents report lapses in receipt of medical home services. In this study, we describe parental experiences with specific medical home components for their children with ASD. We analysed data from all children within the National Survey of Children with Special Health Care Needs database with ASD and a usual place for care (n = 2859). We evaluated the receipt of core medical home components: accessible, comprehensive, coordinated, family centred and compassionate and culturally sensitive care. Children were mean age 10.1 years, and respondents were 75% mothers and 95% reported having a primary care provider (PCP). Seventy-one percent reported care to be usually comprehensive, over three-fourths of respondents reported care to be family centred and compassionate and 87% reported care to be culturally sensitive. Of the parents who reported a need for care coordination (n = 1049), only 14% of parents reported usually getting the help they needed. More educated, English-speaking, non-Hispanic White mothers of older children supported by private insurance were more likely to report never getting as much help coordinating care as desired. Coordination with education services are especially important for children with ASD, yet 27% of parents reported dissatisfaction with PCPs' communication with schools or early intervention. Although parents report a high level of access to PCPs and places for care as well as receiving most core components of the medical home, care coordination activities are lacking for children with ASD. More resourced families are particularly likely to report unmet needs. © 2015 John Wiley & Sons Ltd.

Improving care planning and coordination for service users with medical co-morbidity transitioning between tertiary medical and primary care services.

PubMed

Cranwell, K; Polacsek, M; McCann, T V

2017-08-01

WHAT IS KNOWN ON THE SUBJECT?: Mental health service users with medical co-morbidity frequently experience difficulties accessing and receiving appropriate treatment in emergency departments. Service users frequently experience fragmented care planning and coordinating between tertiary medical and primary care services. Little is known about mental health nurses' perspectives about how to address these problems. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: Emergency department clinicians' poor communication and negative attitudes have adverse effects on service users and the quality of care they receive. The findings contribute to the international evidence about mental health nurses' perspectives of service users feeling confused and frustrated in this situation, and improving coordination and continuity of care, facilitating transitions and increasing family and caregiver participation. Intervention studies are needed to evaluate if adoption of these measures leads to sustainable improvements in care planning and coordination, and how service users with medical co-morbidity are treated in emergency departments in particular. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Effective planning and coordination of care are essential to enable smooth transitions between tertiary medical (emergency departments in particular) and primary care services for service users with medical co-morbidity. Ongoing professional development education and support is needed for emergency department clinicians. There is also a need to develop an organized and systemic approach to improving service users' experience in emergency departments. Introduction Mental health service users with medical co-morbidity frequently experience difficulties accessing appropriate treatment in medical hospitals, and often there is poor collaboration within and between services. Little is known about mental health nurses' perspectives on how to address these problems. Aim To explore mental health nurses' perspectives of the experience of service users with medical co-morbidity in tertiary medical services, and to identify how to improve care planning and coordination for service users transitioning between tertiary medical and primary care services. Method Embedded within an experience-based co-design study, focus group discussions were conducted with 17 emergency department nurses and other clinicians, in Melbourne, Australia. Results Three main themes were abstracted from the data: feeling confused and frustrated, enhancing service users' transition and experience and involving families and caregivers. Participants perceived the service user experience to be characterized by fear, confusion and a sense of not being listened to. They highlighted that service users' transition and experience could be enhanced by facilitating transitions and improving coordination and continuity of care. They also emphasized the need to increase family and caregiver participation. Conclusion Our findings contribute to knowledge about improving the way service users are treated in emergency departments and improving care planning and coordination; in particular, facilitating transitions, improving coordination and continuity of care and increasing family and caregiver participation. © 2016 The Authors. Journal of Psychiatric and Mental Health Nursing Published by John Wiley & Sons Ltd.

"The Doctor Needs to Know": Acceptability of Smartphone Location Tracking for Care Coordination.

PubMed

Liss, David T; Serrano, Eloisa; Wakeman, Julie; Nowicki, Christine; Buchanan, David R; Cesan, Ana; Brown, Tiffany

2018-05-04

Care coordination can be highly challenging to carry out. When care is fragmented across health systems and providers, there is an increased likelihood of hospital readmissions and wasteful health care spending. During and after care transitions, smartphones have the potential to bolster information transfer and care coordination. However, little research has examined patients' perceptions of using smartphones to coordinate care. This study's primary objective was to explore patient acceptability of a smartphone app that could facilitate care coordination in a safety net setting. Our secondary objective was to identify how clinicians and other members of primary care teams could use this app to coordinate care. This qualitative study was conducted at a federally qualified health center in metropolitan Chicago, IL. We conducted four focus groups (two in English, two in Spanish) with high-risk adults who owned a smartphone and received services from an organizational care management program. We also conducted structured interviews with clinicians and a group interview with care managers. Focus groups elicited patients' perceptions of a smartphone app designed to: (1) identify emergency department (ED) visits and inpatient stays using real-time location data; (2) send automated notifications (ie, alerts) to users' phones, asking whether they were a patient in the hospital; and (3) send automated messages to primary care teams to notify them about patients' confirmed ED visits and inpatient stays. Focus group transcripts were coded based on emergent themes. Clinicians and care managers were asked about messages they would like to receive from the app. Five main themes emerged in patient focus group discussions. First, participants expressed a high degree of willingness to use the proposed app during inpatient stays. Second, participants expressed varying degrees of willingness to use the app during ED visits, particularly for low acuity ED visits. Third, participants stated their willingness to have their location tracked by the proposed app due to its perceived benefits. Fourth, the most frequently mentioned barriers to acceptability were inconveniences such as "false alarm" notifications and smartphone battery drainage. Finally, there was some tension between how to maximize usability without unnecessarily increasing user burden. Both clinicians and care managers expressed interest in receiving messages from the app at the time of hospital arrival and at discharge. Clinicians were particularly interested in conducting outreach during ED visits and inpatient stays, while care managers expressed more interest in coordinating postdischarge care. High-risk primary care patients in a safety net setting reported a willingness to utilize smartphone location tracking technology to facilitate care coordination. Further research is needed on the development and implementation of new smartphone-based approaches to care coordination. ©David T Liss, Eloisa Serrano, Julie Wakeman, Christine Nowicki, David R Buchanan, Ana Cesan, Tiffany Brown. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 04.05.2018.

Racial/Ethnic Disparities in Primary Care Quality Among Type 2 Diabetes Patients, Medical Expenditure Panel Survey, 2012.

PubMed

Hu, Ruwei; Shi, Leiyu; Liang, Hailun; Haile, Geraldine Pierre; Lee, De-Chih

2016-08-04

Racial and ethnic disparities exist in diabetes prevalence, access to diabetes care, diabetes-related complications and mortality rates, and the quality of diabetes care among Americans. We explored racial and ethnic disparities in primary care quality among Americans with type 2 diabetes. We analyzed data on adults with type 2 diabetes derived from the household component of the 2012 Medical Expenditure Panel Survey. Multiple regression and multivariate logistic regressions were used to examine the association between race/ethnicity and primary care attributes related to first contact, longitudinality, comprehensiveness, and coordination, and clusters of confounding factors were added sequentially. Preliminary findings indicated differences in primary care quality between racial/ethnic minorities and whites across measures of first contact, longitudinality, comprehensiveness, and coordination. After controlling for confounding factors, these differences were no longer apparent; all racial/ethnic categories showed similar rates of primary care quality according to the 4 primary care domains of interest in the study. Results indicate equitable primary care quality for type 2 diabetes patients across 4 key domains of primary care after controlling for socioeconomic characteristics. Additional research is necessary to support these findings, particularly when considering smaller racial/ethnic groups and investigating outcomes related to diabetes.

The Development and Validation of a Rapid Assessment Tool of Primary Care in China

PubMed Central

Mei, Jie; Liang, Yuan; Shi, LeiYu; Zhao, JingGe; Wang, YuTan; Kuang, Li

2016-01-01

Introduction. With Chinese health care reform increasingly emphasizing the importance of primary care, the need for a tool to evaluate primary care performance and service delivery is clear. This study presents a methodology for a rapid assessment of primary care organizations and service delivery in China. Methods. The study translated and adapted the Primary Care Assessment Tool-Adult Edition (PCAT-AE) into a Chinese version to measure core dimensions of primary care, namely, first contact, continuity, comprehensiveness, and coordination. A cross-sectional survey was conducted to assess the validity and reliability of the Chinese Rapid Primary Care Assessment Tool (CR-PCAT). Eight community health centers in Guangdong province have been selected to participate in the survey. Results. A total of 1465 effective samples were included for data analysis. Eight items were eliminated following principal component analysis and reliability testing. The principal component analysis extracted five multiple-item scales (first contact utilization, first contact accessibility, ongoing care, comprehensiveness, and coordination). The tests of scaling assumptions were basically met. Conclusion. The standard psychometric evaluation indicates that the scales have achieved relatively good reliability and validity. The CR-PCAT provides a rapid and reliable measure of four core dimensions of primary care, which could be applied in various scenarios. PMID:26885509

A Comprehensive Primary Health Care Delivery Model.

ERIC Educational Resources Information Center

Pullen, Carol; And Others

1994-01-01

This primary health care model is based on four assumptions: emphasis on collective, not individual, needs; coordination of preventive/episodic care with secondary/tertiary care; comprehensive, holistic approach; and partnership and equality among professional disciplines and community members. Stakeholders involved are medical, nursing, and…

Microfluidic active mixers employing ultra-high aspect-ratio rare-earth magnetic nano-composite polymer artificial cilia

NASA Astrophysics Data System (ADS)

Rahbar, Mona; Shannon, Lesley; Gray, Bonnie L.

2014-02-01

We present a new micromixer based on highly magnetic, flexible, high aspect-ratio, artificial cilia that are fabricated as individual micromixer elements or in arrays for improved mixing performance. These new cilia enable high efficiency, fast mixing in a microchamber, and are controlled by small electromagnetic fields. The artificial cilia are fabricated using a new micromolding process for nano-composite polymers. Cilia fibers with aspect-ratios as high as 8:0.13 demonstrate the fabrication technique's capability in creating ultra-high aspect-ratio microstructures. Cilia, which are realized in polydimethylsiloxane doped with rare-earth magnetic powder, are magnetized to produce permanent magnetic structures with bidirectional deflection capabilities, making them highly suitable as mixers controlled by electromagnetic fields. Due to the high magnetization level of the polarized nano-composite polymer, we are able to use miniature electromagnets providing relatively small magnetic fields of 1.1 to 7 mT to actuate the cilia microstructures over a very wide motion range. Mixing performances of a single cilium, as well as different arrays of multiple cilia ranging from 2 to 8 per reaction chamber, are characterized and compared with passive diffusion mixing performance. The mixer cilia are actuated at different amplitudes and frequencies to optimize mixing performance. We demonstrate that more than 85% of the total volume of the reaction chamber is fully mixed after 3.5 min using a single cilium mixer at 7 mT compared with only 20% of the total volume mixed with passive diffusion. The time to achieve over 85% mixing is further reduced to 70 s using an array of eight cilia microstructures. The novel microfabrication technique and use of rare-earth permanently-magnetizable nano-composite polymers in mixer applications has not been reported elsewhere by other researchers. We further demonstrate improved mixing over other cilia micromixers as enabled by the high aspect-ratio, high flexibility, and magnetic properties of our cilia micromixer elements.

Enhancing Services to the Rural Elderly through Primary Care Centers.

ERIC Educational Resources Information Center

Leighton, Jeannette; Sprague, Patricia

This paper describes a systematic, coordinated approach to the delivery of health and social services to the rural elderly of Maine provided by the Kennebec Valley Regional Health Agency. Four points of the model are described which distinguish it from other models of coordination: (1) a strong medical orientation in the assessment process; (2)…

Strengthening the Coordination of Pediatric Mental Health and Medical Care: Piloting a Collaborative Model for Freestanding Practices

ERIC Educational Resources Information Center

Greene, Carolyn A.; Ford, Julian D.; Ward-Zimmerman, Barbara; Honigfeld, Lisa; Pidano, Anne E.

2016-01-01

Background: Collaborative pediatric mental health and primary care is increasingly recognized as optimal for meeting the needs of children with mental health problems. This paper describes the challenges faced by freestanding specialty mental health clinics and pediatric health practices to provide such coordinated mind-and-body treatment. It…

Natural Systems: MINNEMAST Coordinated Mathematics - Science Series, Unit 29.

ERIC Educational Resources Information Center

Bakke, Jeannette; And Others

This volume is the last in a series of 29 coordinated MINNEMAST units in mathematics and science for kindergarten and the primary grades. Intended for use by third-grade teachers, this unit guide provides a summary and overview of the unit, a list of materials needed, and descriptions of three groups of lessons. The purposes and procedures for…

Infant Vocal-Motor Coordination: Precursor to the Gesture-Speech System?

ERIC Educational Resources Information Center

Iverson, Jana M.; Fagan, Mary K.

2004-01-01

This study was designed to provide a general picture of infant vocal-motor coordination and test predictions generated by Iverson and Thelen's (1999) model of the development of the gesture-speech system. Forty-seven 6- to 9-month-old infants were videotaped with a primary caregiver during rattle and toy play. Results indicated an age-related…

Technology Leadership or Technology Somnambulism? Exploring the Discourse of Integration amongst Information and Communication Technology Coordinators

ERIC Educational Resources Information Center

McDonagh, Adrian; McGarr, Oliver

2015-01-01

This research aimed to explore information and communication technology (ICT) coordinators' discourse in relation to ICT integration in a sample of Irish post-primary schools. As ICT leaders in their schools, how they conceptualise ICT significantly influences school-based policy and use. The research involved semi-structured interviews with a…

Focus groups to explore healthcare professionals' experiences of care coordination: towards a theoretical framework for the study of care coordination.

PubMed

Van Houdt, Sabine; Sermeus, Walter; Vanhaecht, Kris; De Lepeleire, Jan

2014-12-24

Strategies to improve care coordination between primary and hospital care do not always have the desired results. This is partly due to incomplete understanding of the key concepts of care coordination. An in-depth analysis of existing theoretical frameworks for the study of care coordination identified 14 interrelated key concepts. In another study, these 14 key concepts were further explored in patients' experiences. Additionally, "patient characteristics" was identified as a new key concept in patients' experiences and the previously identified key concept "quality of relationship" between healthcare professionals was extended to "quality of relationship" with the patient. Together, these 15 interrelated key concepts resulted in a new theoretical framework. The present study aimed at improving our understanding of the 15 previously identified key concepts and to explore potentially previous unidentified key concepts and the links between these by exploring how healthcare professionals experience care coordination. A qualitative design was used. Six focus groups were conducted including primary healthcare professionals involved in the care of patients who had breast cancer surgery at three hospitals in Belgium. Data were analyzed using constant comparative analysis. All 15 previously identified key concepts of care coordination were further explored in healthcare professionals' experiences. Links between these 15 concepts were identified, including 9 newly identified links. The concept "external factors" was linked with all 6 concepts relating to (inter)organizational mechanisms; "task characteristics", "structure", "knowledge and information technology", "administrative operational processes", "cultural factors" and "need for coordination". Five of these concepts related to 3 concepts of relational coordination; "roles", "quality of relationship" and "exchange of information". The concept of "task characteristics" was only linked with "roles" and "exchange of information". The concept "patient characteristics" related with the concepts "need for coordination" and "patient outcome". Outcome was influenced by "roles", "quality of relationship" and "exchange of information". External factors and the (inter)organizational mechanism should enhance "roles" and "quality of relationship" between healthcare professionals and with the patient as well as "exchange of information", and setting and sharing of common "goals" to improve care coordination and quality of care.

Impact of a low intensity and broadly inclusive ED care coordination intervention on linkage to primary care and ED utilization.

PubMed

Foster, Sean D; Hart, Kim; Lindsell, Christopher J; Miller, Christopher N; Lyons, Michael S

2018-04-05

We aim to evaluate the effectiveness of a broadly inclusive, comparatively low intensity intervention linking ED patients to a primary care home. This retrospective cohort study evaluated ED patients referred for primary care linkage in a large, urban, academic ED. A care coordination specialist performed a brief interview to gauge access barriers and provide a clinic referral with optional scheduling assistance. Data were abstracted from program records and the electronic medical record. The primary outcome was the proportion of referred individuals who attended at least one primary care appointment. Secondary outcomes included return ED encounters within one year, and factors associated with linkage outcomes. There were 2142 referrals made for 2064 patients; 1688/2142 accepted assistance. Linkage was successful for 1059/1688 (63%, CI95 60% to 65%). Among patients accepting assistance, those without successful linkage were younger (41 vs 45years, difference 3years, CI95 2 to 3), more often male (62% vs 55%,difference 7%, CI95 2% to 12%), and less likely to have a chronic medical condition (37% vs 45%, difference 8%; CI95 3% to 12%) or to have had an appointment scheduled within two weeks (26% vs 33%, difference 7%, CI95 2% to 12%). Insurance status and self-reported barriers to care were not associated with linkage success. Patterns of subsequent ED use were similar, regardless of referral status or linkage outcome. Low intensity, broadly inclusive, ED care coordination linked nearly 50% of patients referred for intervention, and two-thirds of willing participants, with a primary care home. Copyright © 2018 Elsevier Inc. All rights reserved.

Improving home-based providers' communication to primary care providers to enhance care coordination.

PubMed

Gum, Amber M; Dautovich, Natalie D; Greene, Jennifer; Hirsch, Anne; Schonfeld, Lawrence

2015-01-01

Health care system fragmentation is a pervasive problem. Research has not delineated concrete behavioral strategies to guide providers to communicate with personnel in other organizations to coordinate care. We addressed this gap within a particular context: home-based providers delivering depression care management (DCM) to older adults requiring coordination with primary care personnel. Our objective was to pilot test a communication protocol ('BRIDGE - BRinging Inter-Disciplinary Guidelines to Elders') in conjunction with DCM. In an open pilot trial (N = 7), home-based providers delivered DCM to participants. Following the BRIDGE protocol, home-based providers made scripted telephone calls and sent structured progress reports to personnel in participants' primary care practices with concise information and requests for assistance. Home-based providers documented visits with participants, contacts to and responses from primary care personnel. A research interviewer assessed participant outcomes [Symptom Checklist-20 (depressive symptoms), World Health Organization Disability Assessment Schedule-12, satisfaction] at baseline, three months, and six months. Over 12 months, home-based providers made 2.4 telephone calls and sent 6.3 faxes to other personnel, on average per participant. Primary care personnel responded to 18 of 22 requests (81.8%; 2 requests dropped, 2 ongoing), with at least one response per participant. Participants' depressive symptoms and disability improved significantly at both post-tests with large effect sizes (d ranged 0.73-2.3). Participants were satisfied. Using BRIDGE, home-based providers expended a small amount of effort to communicate with primary care personnel, who responded to almost all requests. Larger scale research is needed to confirm findings and potentially extend BRIDGE to other client problems, professions, and service sectors.

Difference method to search for the anisotropy of primary cosmic radiation

NASA Astrophysics Data System (ADS)

Pavlyuchenko, V. P.; Martirosov, R. M.; Nikolskaya, N. M.; Erlykin, A. D.

2018-01-01

The original difference method used in the search for an anisotropy of primary cosmic radiation at the knee region of its energy spectrum is considered. Its methodical features and properties are analyzed. It is shown that this method, in which properties of particle fluxes (rather than an intensity) are investigated, is stable against random experimental errors and allows one to separate anomalies connected with the laboratory coordinate system from anomalies in the celestial coordinate system. The method uses the multiple scattering of charged particles in the magnetic fields of the Galaxy to study the whole celestial sphere, including the regions outside the line of sight of the installation.

The search of the anisotropy of the primary cosmic radiation by the difference method

NASA Astrophysics Data System (ADS)

Pavlyuchenko, Victor; Martirosov, Romen; Nikolskaya, Natalia; Erlykin, Anatoly

2017-06-01

On the basis of experimental data obtained in the knee energy region with the GAMMA array an anomaly has been found in the mass composition of primary cosmic rays coming from the region of the VELA cluster. We used an original difference method which has high sensitivity, stability against accidental experimental errors and the possibility to separate anomalies connected with the laboratory coordinate system from anomalies observed in the celestial coordinates. The multiple scattering of the charged particles in the galactic magnetic fields makes it possible to study regions of the sky outside the direct visibility of the array.

Linking the Medical and Educational Home to Support Children With Autism Spectrum Disorder: Practice Recommendations.

PubMed

Shahidullah, Jeffrey D; Azad, Gazi; Mezher, Katherine R; McClain, Maryellen Brunson; McIntyre, Laura Lee

2018-05-01

Children with autism spectrum disorder (ASD) present with complex medical problems that are often exacerbated by a range of other intellectual and psychiatric comorbidities. These children receive care for their physical and mental health from a range of providers within numerous child-serving systems, including their primary care clinic, school, and the home and community. Given the longitudinal nature in which care is provided for this chronic disorder, it is particularly necessary for services and providers to coordinate their care to ensure optimal efficiency and effectiveness. There are 2 primary venues that serve as a "home" for coordination of service provision for children with ASD and their families-the "medical home" and the "educational home." Unfortunately, these venues often function independently from the other. Furthermore, there are limited guidelines demonstrating methods through which pediatricians and other primary care providers (PCPs) can coordinate care with schools and school-based providers. The purpose of this article is 2-fold: (1) we highlight the provision of evidence-based care within the medical home and educational home and (2) we offer practice recommendations for PCPs in integrating these systems to optimally address the complex medical, intellectual, and psychiatric symptomology affected by autism.

Potential Mechanisms Underlying Intercortical Signal Regulation via Cholinergic Neuromodulators

PubMed Central

Whittington, Miles A.; Kopell, Nancy J.

2015-01-01

The dynamical behavior of the cortex is extremely complex, with different areas and even different layers of a cortical column displaying different temporal patterns. A major open question is how the signals from different layers and different brain regions are coordinated in a flexible manner to support function. Here, we considered interactions between primary auditory cortex and adjacent association cortex. Using a biophysically based model, we show how top-down signals in the beta and gamma regimes can interact with a bottom-up gamma rhythm to provide regulation of signals between the cortical areas and among layers. The flow of signals depends on cholinergic modulation: with only glutamatergic drive, we show that top-down gamma rhythms may block sensory signals. In the presence of cholinergic drive, top-down beta rhythms can lift this blockade and allow signals to flow reciprocally between primary sensory and parietal cortex. SIGNIFICANCE STATEMENT Flexible coordination of multiple cortical areas is critical for complex cognitive functions, but how this is accomplished is not understood. Using computational models, we studied the interactions between primary auditory cortex (A1) and association cortex (Par2). Our model is capable of replicating interaction patterns observed in vitro and the simulations predict that the coordination between top-down gamma and beta rhythms is central to the gating process regulating bottom-up sensory signaling projected from A1 to Par2 and that cholinergic modulation allows this coordination to occur. PMID:26558772

Mechanosensory Genes Pkd1 and Pkd2 Contribute to the Planar Polarization of Brain Ventricular Epithelium

PubMed Central

Herranz-Pérez, Vicente; Nakatani, Jin; Boletta, Alessandra; García-Verdugo, José Manuel

2015-01-01

Directional beating of ependymal (E) cells' cilia in the walls of the ventricles in the brain is essential for proper CSF flow. E cells display two forms of planar cell polarity (PCP): rotational polarity of individual cilium and translational polarity (asymmetric positioning of cilia in the apical area). The orientation of individual E cells varies according to their location in the ventricular wall (location-specific PCP). It has been hypothesized that hydrodynamic forces on the apical surface of radial glia cells (RGCs), the embryonic precursors of E cells, could guide location-specific PCP in the ventricular epithelium. However, the detection mechanisms for these hydrodynamic forces have not been identified. Here, we show that the mechanosensory proteins polycystic kidney disease 1 (Pkd1) and Pkd2 are present in primary cilia of RGCs. Ablation of Pkd1 or Pkd2 in Nestin-Cre;Pkd1flox/flox or Nestin-Cre;Pkd2flox/flox mice, affected PCP development in RGCs and E cells. Early shear forces on the ventricular epithelium may activate Pkd1 and Pkd2 in primary cilia of RGCs to properly polarize RGCs and E cells. Consistently, Pkd1, Pkd2, or primary cilia on RGCs were required for the proper asymmetric localization of the PCP protein Vangl2 in E cells' apical area. Analyses of single- and double-heterozygous mutants for Pkd1 and/or Vangl2 suggest that these genes function in the same pathway to establish E cells' PCP. We conclude that Pkd1 and Pkd2 mechanosensory proteins contribute to the development of brain PCP and prevention of hydrocephalus. SIGNIFICANCE STATEMENT This study identifies key molecules in the development of planar cell polarity (PCP) in the brain and prevention of hydrocephalus. Multiciliated ependymal (E) cells within the brain ventricular epithelium generate CSF flow through ciliary beating. E cells display location-specific PCP in the orientation and asymmetric positioning of their cilia. Defects in this PCP can result in hydrocephalus. Hydrodynamic forces on radial glial cells (RGCs), the embryonic progenitors of E cells, have been suggested to guide PCP. We show that the mechanosensory proteins Pkd1 and Pkd2 localize to primary cilia in RGCs, and their ablation disrupts the development of PCP in E cells. Early shear forces on RGCs may activate Pkd1 and Pkd2 in RGCs' primary cilia to properly orient E cells. This study identifies key molecules in the development of brain PCP and prevention of hydrocephalus. PMID:26245976

Rural-to-Urban Migrants' Experiences with Primary Care under Different Types of Medical Institutions in Guangzhou, China

PubMed Central

Zeng, Jiazhi; Shi, Leiyu; Zou, Xia; Chen, Wen; Ling, Li

2015-01-01

Objectives China is facing the unprecedented challenge of rapidly increasing rural-to-urban migration. Migrants are in a vulnerable state when they attempt to access to primary care services. This study was designed to explore rural-to-urban migrants’ experiences in primary care, comparing their quality of primary care experiences under different types of medical institutions in Guangzhou, China. Methods The study employed a cross-sectional survey of 736 rural-to-urban migrants in Guangzhou, China in 2014. A validated Chinese version of Primary Care Assessment Tool—Adult Short Version (PCAT-AS), representing 10 primary care domains was used to collect information on migrants’ quality of primary care experiences. These domains include first contact (utilization), first contact (accessibility), ongoing care, coordination (referrals), coordination (information systems), comprehensiveness (services available), comprehensiveness (services provided), family-centeredness, community orientation and culturally competent. These measures were used to assess the quality of primary care performance as reported from patients’ perspective. Analysis of covariance was conducted for comparison on PCAT scores among migrants accessing primary care in tertiary hospitals, municipal hospitals, community health centers/community health stations, and township health centers/rural health stations. Multiple linear regression models were used to explore factors associated with PCAT total scores. Results After adjustments were made, migrants accessing primary care in tertiary hospitals (25.49) reported the highest PCAT total scores, followed by municipal hospitals (25.02), community health centers/community health stations (24.24), and township health centers/rural health stations (24.18). Tertiary hospital users reported significantly better performance in first contact (utilization), first contact (accessibility), coordination (information system), comprehensiveness (service available), and cultural competence. Community health center/community health station users reported significantly better experience in the community orientation domain. Township health center/rural health station users expressed significantly better experience in the ongoing care domain. There were no statistically significant differences across settings in the ongoing care, comprehensiveness (services provided), and family-centeredness domains. Multiple linear regression models showed that factors positively associated with higher PCAT total scores also included insurance covering parts of healthcare payment (P<0.001). Conclusions This study highlights the need for improvement in primary care provided by primary care institutions for rural-to-urban migrants. Relevant policies related to medical insurance should be implemented for providing affordable healthcare services for migrants accessing primary care. PMID:26474161

Functional characterization of the vertebrate primary ureter: Structure and ion transport mechanisms of the pronephric duct in axolotl larvae (Amphibia)

PubMed Central

2010-01-01

Background Three kidney systems appear during vertebrate development: the pronephroi, mesonephroi and metanephroi. The pronephric duct is the first or primary ureter of these kidney systems. Its role as a key player in the induction of nephrogenic mesenchyme is well established. Here we investigate whether the duct is involved in urine modification using larvae of the freshwater amphibian Ambystoma mexicanum (axolotl) as model. Results We investigated structural as well as physiological properties of the pronephric duct. The key elements of our methodology were: using histology, light and transmission electron microscopy as well as confocal laser scanning microscopy on fixed tissue and applying the microperfusion technique on isolated pronephric ducts in combination with single cell microelectrode impalements. Our data show that the fully differentiated pronephric duct is composed of a single layered epithelium consisting of one cell type comparable to the principal cell of the renal collecting duct system. The cells are characterized by a prominent basolateral labyrinth and a relatively smooth apical surface with one central cilium. Cellular impalements demonstrate the presence of apical Na+ and K+ conductances, as well as a large K+ conductance in the basolateral cell membrane. Immunolabeling experiments indicate heavy expression of Na+/K+-ATPase in the basolateral labyrinth. Conclusions We propose that the pronephric duct is important for the subsequent modification of urine produced by the pronephros. Our results indicate that it reabsorbs sodium and secretes potassium via channels present in the apical cell membrane with the driving force for ion movement provided by the Na+/K+ pump. This is to our knowledge the first characterization of the pronephric duct, the precursor of the collecting duct system, which provides a model of cell structure and basic mechanisms for ion transport. Such information may be important in understanding the evolution of vertebrate kidney systems and human diseases associated with congenital malformations. PMID:20507566

Arsenic inhibits hedgehog signaling during P19 cell differentiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Jui Tung; Bain, Lisa J., E-mail: lbain@clemson.edu; Department of Biological Sciences, Clemson University, 132 Long Hall, Clemson, SC 29634

Arsenic is a toxicant found in ground water around the world, and human exposure mainly comes from drinking water or from crops grown in areas containing arsenic in soils or water. Epidemiological studies have shown that arsenic exposure during development decreased intellectual function, reduced birth weight, and altered locomotor activity, while in vitro studies have shown that arsenite decreased muscle and neuronal cell differentiation. The sonic hedgehog (Shh) signaling pathway plays an important role during the differentiation of both neurons and skeletal muscle. The purpose of this study was to investigate whether arsenic can disrupt Shh signaling in P19 mousemore » embryonic stem cells, leading to changes muscle and neuronal cell differentiation. P19 embryonic stem cells were exposed to 0, 0.25, or 0.5 μM of sodium arsenite for up to 9 days during cell differentiation. We found that arsenite exposure significantly reduced transcript levels of genes in the Shh pathway in both a time and dose-dependent manner. This included the Shh ligand, which was decreased 2- to 3-fold, the Gli2 transcription factor, which was decreased 2- to 3-fold, and its downstream target gene Ascl1, which was decreased 5-fold. GLI2 protein levels and transcriptional activity were also reduced. However, arsenic did not alter GLI2 primary cilium accumulation or nuclear translocation. Moreover, additional extracellular SHH rescued the inhibitory effects of arsenic on cellular differentiation due to an increase in GLI binding activity. Taken together, we conclude that arsenic exposure affected Shh signaling, ultimately decreasing the expression of the Gli2 transcription factor. These results suggest a mechanism by which arsenic disrupts cell differentiation. - Highlights: • Arsenic exposure decreases sonic hedgehog pathway-related gene expression. • Arsenic decreases GLI2 protein levels and transcriptional activity in P19 cells. • Arsenic exposure does not alter the levels of SHH expression and GLI2 primary cilum accumulation. • Induction of the Shh pathway rescues arsenic's inhibitory effects on cell differentiation.« less

Mutation of Growth Arrest Specific 8 Reveals a Role in Motile Cilia Function and Human Disease

PubMed Central

Lewis, Wesley R.; Malarkey, Erik B.; Tritschler, Douglas; Bower, Raqual; Pasek, Raymond C.; Porath, Jonathan D.; Birket, Susan E.; Saunier, Sophie; Antignac, Corinne; Leigh, Margaret W.; Zariwala, Maimoona A.; Drummond, Iain A.; Parant, John M.; Hildebrandt, Friedhelm; Yoder, Bradley K.

2016-01-01

Ciliopathies are genetic disorders arising from dysfunction of microtubule-based cellular appendages called cilia. Different cilia types possess distinct stereotypic microtubule doublet arrangements with non-motile or ‘primary’ cilia having a 9+0 and motile cilia have a 9+2 array of microtubule doublets. Primary cilia are critical sensory and signaling centers needed for normal mammalian development. Defects in their structure/function result in a spectrum of clinical and developmental pathologies including abnormal neural tube and limb patterning. Altered patterning phenotypes in the limb and neural tube are due to perturbations in the hedgehog (Hh) signaling pathway. Motile cilia are important in fluid movement and defects in motility result in chronic respiratory infections, altered left-right asymmetry, and infertility. These features are the hallmarks of Primary Ciliary Dyskinesia (PCD, OMIM 244400). While mutations in several genes are associated with PCD in patients and animal models, the genetic lesion in many cases is unknown. We assessed the in vivo functions of Growth Arrest Specific 8 (GAS8). GAS8 shares strong sequence similarity with the Chlamydomonas Nexin-Dynein Regulatory Complex (NDRC) protein 4 (DRC4) where it is needed for proper flagella motility. In mammalian cells, the GAS8 protein localizes not only to the microtubule axoneme of motile cilia, but also to the base of non-motile cilia. Gas8 was recently implicated in the Hh signaling pathway as a regulator of Smoothened trafficking into the cilium. Here, we generate the first mouse with a Gas8 mutation and show that it causes severe PCD phenotypes; however, there were no overt Hh pathway phenotypes. In addition, we identified two human patients with missense variants in Gas8. Rescue experiments in Chlamydomonas revealed a subtle defect in swim velocity compared to controls. Further experiments using CRISPR/Cas9 homology driven repair (HDR) to generate one of these human missense variants in mice demonstrated that this allele is likely pathogenic. PMID:27472056

Curriculum Guide for Day Care Primary.

ERIC Educational Resources Information Center

Radke, Mary Ann

This curriculum, designed for severely retarded children in a primary day care setting, is divided into three sections: (1) Awareness of Body Parts, (2) Gross Motor Skills, and (3) Language Arts. Detailed activities are suggested to develop and reinforce various gross motor coordinations and learning skills. (CS)

Apparatus and method for mapping an area of interest

DOEpatents

Staab, Torsten A. Cohen, Daniel L.; Feller, Samuel [Fairfax, VA

2009-12-01

An apparatus and method are provided for mapping an area of interest using polar coordinates or Cartesian coordinates. The apparatus includes a range finder, an azimuth angle measuring device to provide a heading and an inclinometer to provide an angle of inclination of the range finder as it relates to primary reference points and points of interest. A computer is provided to receive signals from the range finder, inclinometer and azimuth angle measurer to record location data and calculate relative locations between one or more points of interest and one or more primary reference points. The method includes mapping of an area of interest to locate points of interest relative to one or more primary reference points and to store the information in the desired manner. The device may optionally also include an illuminator which can be utilized to paint the area of interest to indicate both points of interest and primary points of reference during and/or after data acquisition.

Research on Synchronous Coordination Development of Tourism-Economy-Environment System in Qinghai Section of Silk Road

NASA Astrophysics Data System (ADS)

Xue, Huaju

2018-01-01

Using coupling theory in physics, the paper analyzed the relationship of coordinated development of tourism-economy-environment system (abbr. TEES) in Qinghai. Results showed the comprehensive evaluation of Qinghai TEES has been improved greatly from 2000 to 2014. However, coupling degree has still been in the running-in stage and coordination degree only arrives at the primary coordination level, the development of economy and tourism has exceeded the threshold of ecological environment after 2008, and the ecological environment has become the bottleneck restricting the further improvement of coupling coordination. In the future, Qinghai must change its mode of development and focus on industrial upgrading and transformation so as to promote the harmonious and sustainable development of TEES in the Silk Road.

A Research Agenda to Advance the Coordination of Care for General Medical and Substance Use Disorders.

PubMed

Quinn, Amity E; Rubinsky, Anna D; Fernandez, Anne C; Hahm, Hyeouk Chris; Samet, Jeffrey H

2017-04-01

The separation of addiction care from the general medical care system has a negative impact on patients' receipt of high-quality medical care. Clinical and policy-level strategies to improve the coordination of addiction care and general medical care include identifying and engaging patients with unhealthy substance use in general medical settings, providing effective chronic disease management of substance use disorders in primary care, including patient and family perspectives in care coordination, and implementing pragmatic models to pay for the coordination of addiction and general medical care. This Open Forum discusses practice and research recommendations to advance the coordination of general medical and addiction care. The discussion is based on the proceedings of a national meeting of experts in 2014.

Analysis of zinc binding sites in protein crystal structures.

PubMed

Alberts, I L; Nadassy, K; Wodak, S J

1998-08-01

The geometrical properties of zinc binding sites in a dataset of high quality protein crystal structures deposited in the Protein Data Bank have been examined to identify important differences between zinc sites that are directly involved in catalysis and those that play a structural role. Coordination angles in the zinc primary coordination sphere are compared with ideal values for each coordination geometry, and zinc coordination distances are compared with those in small zinc complexes from the Cambridge Structural Database as a guide of expected trends. We find that distances and angles in the primary coordination sphere are in general close to the expected (or ideal) values. Deviations occur primarily for oxygen coordinating atoms and are found to be mainly due to H-bonding of the oxygen coordinating ligand to protein residues, bidentate binding arrangements, and multi-zinc sites. We find that H-bonding of oxygen containing residues (or water) to zinc bound histidines is almost universal in our dataset and defines the elec-His-Zn motif. Analysis of the stereochemistry shows that carboxyl elec-His-Zn motifs are geometrically rigid, while water elec-His-Zn motifs show the most geometrical variation. As catalytic motifs have a higher proportion of carboxyl elec atoms than structural motifs, they provide a more rigid framework for zinc binding. This is understood biologically, as a small distortion in the zinc position in an enzyme can have serious consequences on the enzymatic reaction. We also analyze the sequence pattern of the zinc ligands and residues that provide elecs, and identify conserved hydrophobic residues in the endopeptidases that also appear to contribute to stabilizing the catalytic zinc site. A zinc binding template in protein crystal structures is derived from these observations.

Building Student and Family-Centered Care Coordination Through Ongoing Delivery System Design.

PubMed

Baker, Dian; Anderson, Lori; Johnson, Jody

2017-01-01

In 2016 the National Association of School Nurses released an updated framework for school nurse practice. One highlight of the new framework is 21st century care coordination. That is, moving beyond basic case management to a systems-level approach for delivery of school health services. The framework broadly applies the term care coordination to include direct care and communication across systems. School nurses are often engaged in efforts to create school health care homes that serve as an axis of coordination for students and families between primary care offices and the schools. Effective care coordination requires that the school nurses not only know the principles of traditional case management but also understand complex systems that drive effective care coordination. The outcome of a system-level approach is enhanced access to services in an integrated health care delivery system that includes the school nurse as an integral member of the school's health care team. This article presents a comprehensive, system-level model of care coordination for school nurse leadership and practice.

Optimizing Patient-centered Communication and Multidisciplinary Care Coordination in Emergency Diagnostic Imaging: A Research Agenda.

PubMed

Sabbatini, Amber K; Merck, Lisa H; Froemming, Adam T; Vaughan, William; Brown, Michael D; Hess, Erik P; Applegate, Kimberly E; Comfere, Nneka I

2015-12-01

Patient-centered emergency diagnostic imaging relies on efficient communication and multispecialty care coordination to ensure optimal imaging utilization. The construct of the emergency diagnostic imaging care coordination cycle with three main phases (pretest, test, and posttest) provides a useful framework to evaluate care coordination in patient-centered emergency diagnostic imaging. This article summarizes findings reached during the patient-centered outcomes session of the 2015 Academic Emergency Medicine consensus conference "Diagnostic Imaging in the Emergency Department: A Research Agenda to Optimize Utilization." The primary objective was to develop a research agenda focused on 1) defining component parts of the emergency diagnostic imaging care coordination process, 2) identifying gaps in communication that affect emergency diagnostic imaging, and 3) defining optimal methods of communication and multidisciplinary care coordination that ensure patient-centered emergency diagnostic imaging. Prioritized research questions provided the framework to define a research agenda for multidisciplinary care coordination in emergency diagnostic imaging. © 2015 by the Society for Academic Emergency Medicine.

School Mathematics Leaders' Beliefs about Their Role When Participating in a School Mathematics Project

ERIC Educational Resources Information Center

Sexton, Matt; Downton, Ann

2014-01-01

It is not uncommon in many Australian primary schools for a teaching staff member to undertake the leadership or coordination of mathematics in his or her school. Some research (e.g., Cheeseman & Clarke, 2005) suggests that coordinators and leaders play an important role in the leadership and management of mathematics teaching and learning in…

Classroom Behaviour Management Strategies in Response to Problematic Behaviours of Primary School Children with Special Educational Needs: Views of Special Educational Needs Coordinators

ERIC Educational Resources Information Center

Nye, Elizabeth; Gardner, Frances; Hansford, Lorraine; Edwards, Vanessa; Hayes, Rachel; Ford, Tamsin

2016-01-01

Children identified with special educational needs (SEN) and behavioural difficulties present extra challenges to educators and require additional supports in school. This paper presents views from special educational needs coordinators (SENCos) on various strategies used by educators to support children identified with SEN and problematic…

Nurses' Use and Perception of an Information and Communication Technology System for Improving Coordination During Hospital Discharges: A Survey in Swedish Primary Healthcare.

PubMed

Christiansen, Line; Fagerström, Cecilia; Nilsson, Lina

2017-07-01

To facilitate communications between care levels and improve coordination during hospital discharges, there is great potential in using information and communication technology systems, because they can significantly help to deter unnecessary readmissions. However, there is still a lack of knowledge about how often nurses use information and communication technology and the indicators related to its use. The aims of this study were to describe the indicators related to nurses' use of an information and communication technology system for collaboration between care levels and to estimate whether the level of use can be related to nurses' perceptions of the information and communication technology system's contribution to improve coordination during hospital discharges. A quantitative survey of 37 nurses from 11 primary healthcare centers was performed in a county in southern Sweden. The data were analyzed using descriptive and comparative analyses. The results showed that perceptions concerning the information and communication technology system's usability and time consumption differed between nurses who used the system and those who did not. Simultaneously, the nurses were rather unaware of the ability of the information and communication technology system to improve coordination during patient discharges.

Disease-specific clinical pathways - are they feasible in primary care? A mixed-methods study.

PubMed

Grimsmo, Anders; Løhre, Audhild; Røsstad, Tove; Gjerde, Ingunn; Heiberg, Ina; Steinsbekk, Aslak

2018-06-01

To explore the feasibility of disease-specific clinical pathways when used in primary care. A mixed-method sequential exploratory design was used. First, merging and exploring quality interview data across two cases of collaboration between the specialist care and primary care on the introduction of clinical pathways for four selected chronic diseases. Secondly, using quantitative data covering a population of 214,700 to validate and test hypothesis derived from the qualitative findings. Primary care and specialist care collaborating to manage care coordination. Primary-care representatives expressed that their patients often have complex health and social needs that clinical pathways guidelines seldom consider. The representatives experienced that COPD, heart failure, stroke and hip fracture, frequently seen in hospitals, appear in low numbers in primary care. The quantitative study confirmed the extensive complexity among home healthcare nursing patients and demonstrated that, for each of the four selected diagnoses, a homecare nurse on average is responsible for preparing reception of the patient at home after discharge from hospital, less often than every other year. The feasibility of disease-specific pathways in primary care is limited, both from a clinical and organisational perspective, for patients with complex needs. The low prevalence in primary care of patients with important chronic conditions, needing coordinated care after hospital discharge, constricts transferring tasks from specialist care. Generic clinical pathways are likely to be more feasible and efficient for patients in this setting. Key points Clinical pathways in hospitals apply to single-disease guidelines, while more than 90% of the patients discharged to community health care for follow-up have multimorbidity. Primary care has to manage the health care of the patient holistically, with all his or her complex needs. Patients most frequently admitted to hospitals, i.e. patients with COPD, heart failure, stroke and hip fracture are infrequent in primary care and represent a minority among patients in need of coordinated community health care. In primary care, the low rate of receiving patients discharged from hospitals of major chronic diseases hampers maintenance of required specific skills, thus constricting the transfer of tasks to primary care. Generic clinical pathways are suggested to be more feasible than disease-specific pathways for most patients with complex needs.

CELSR2, encoding a planar cell polarity protein, is a putative gene in Joubert syndrome with cortical heterotopia, microophthalmia, and growth hormone deficiency.

PubMed

Vilboux, Thierry; Malicdan, May Christine V; Roney, Joseph C; Cullinane, Andrew R; Stephen, Joshi; Yildirimli, Deniz; Bryant, Joy; Fischer, Roxanne; Vemulapalli, Meghana; Mullikin, James C; Steinbach, Peter J; Gahl, William A; Gunay-Aygun, Meral

2017-03-01

Joubert syndrome is a ciliopathy characterized by a specific constellation of central nervous system malformations that result in the pathognomonic "molar tooth sign" on imaging. More than 27 genes are associated with Joubert syndrome, but some patients do not have mutations in any of these genes. Celsr1, Celsr2, and Celsr3 are the mammalian orthologues of the drosophila planar cell polarity protein, flamingo; they play important roles in neural development, including axon guidance, neuronal migration, and cilium polarity. Here, we report bi-allelic mutations in CELSR2 in a Joubert patient with cortical heterotopia, microophthalmia, and growth hormone deficiency. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

PhotoGate microscopy: tracking single molecules in a cytoplasm (Conference Presentation)

NASA Astrophysics Data System (ADS)

Yildiz, Ahmet

2016-02-01

Tracking single molecules inside cells reveals the dynamics of biological processes, including receptor trafficking, signaling and cargo transport. However, individual molecules often cannot be resolved inside cells due to their high density in the cellular environment. We developed a photobleaching gate assay, which controls the number of fluorescent particles in a region of interest by repeatedly photobleaching its boundary. Using this method, we tracked single particles at surface densities two orders of magnitude higher than the single-molecule detection limit. We observed ligand-induced dimerization of epidermal growth factor receptors (EGFR) on a live cell membrane. In addition, we tracked individual intraflagellar transport (IFT) trains along the length of a cilium and observed their remodeling at the ciliary tip.

The Lipid Raft Proteome of African Trypanosomes Contains Many Flagellar Proteins.

PubMed

Sharma, Aabha I; Olson, Cheryl L; Engman, David M

2017-08-24

Lipid rafts are liquid-ordered membrane microdomains that form by preferential association of 3-β-hydroxysterols, sphingolipids and raft-associated proteins often having acyl modifications. We isolated lipid rafts of the protozoan parasite Trypanosoma brucei and determined the protein composition of lipid rafts in the cell. This analysis revealed a striking enrichment of flagellar proteins and several putative signaling proteins in the lipid raft proteome. Calpains and intraflagellar transport proteins, in particular, were found to be abundant in the lipid raft proteome. These findings provide additional evidence supporting the notion that the eukaryotic cilium/flagellum is a lipid raft-enriched specialized structure with high concentrations of sterols, sphingolipids and palmitoylated proteins involved in environmental sensing and cell signaling.

The Lipid Raft Proteome of African Trypanosomes Contains Many Flagellar Proteins

PubMed Central

Sharma, Aabha I.; Olson, Cheryl L.; Engman, David M.

2017-01-01

Lipid rafts are liquid-ordered membrane microdomains that form by preferential association of 3-β-hydroxysterols, sphingolipids and raft-associated proteins often having acyl modifications. We isolated lipid rafts of the protozoan parasite Trypanosoma brucei and determined the protein composition of lipid rafts in the cell. This analysis revealed a striking enrichment of flagellar proteins and several putative signaling proteins in the lipid raft proteome. Calpains and intraflagellar transport proteins, in particular, were found to be abundant in the lipid raft proteome. These findings provide additional evidence supporting the notion that the eukaryotic cilium/flagellum is a lipid raft-enriched specialized structure with high concentrations of sterols, sphingolipids and palmitoylated proteins involved in environmental sensing and cell signaling. PMID:28837104

Swimming like algae: biomimetic soft artificial cilia

PubMed Central

Sareh, Sina; Rossiter, Jonathan; Conn, Andrew; Drescher, Knut; Goldstein, Raymond E.

2013-01-01

Cilia are used effectively in a wide variety of biological systems from fluid transport to thrust generation. Here, we present the design and implementation of artificial cilia, based on a biomimetic planar actuator using soft-smart materials. This actuator is modelled on the cilia movement of the alga Volvox, and represents the cilium as a piecewise constant-curvature robotic actuator that enables the subsequent direct translation of natural articulation into a multi-segment ionic polymer metal composite actuator. It is demonstrated how the combination of optimal segmentation pattern and biologically derived per-segment driving signals reproduce natural ciliary motion. The amenability of the artificial cilia to scaling is also demonstrated through the comparison of the Reynolds number achieved with that of natural cilia. PMID:23097503

The Coordination Dynamics of Observational Learning: Relative Motion Direction and Relative Phase as Informational Content Linking Action-Perception to Action-Production.

PubMed

Buchanan, John J

2016-01-01

The primary goal of this chapter is to merge together the visual perception perspective of observational learning and the coordination dynamics theory of pattern formation in perception and action. Emphasis is placed on identifying movement features that constrain and inform action-perception and action-production processes. Two sources of visual information are examined, relative motion direction and relative phase. The visual perception perspective states that the topological features of relative motion between limbs and joints remains invariant across an actor's motion and therefore are available for pickup by an observer. Relative phase has been put forth as an informational variable that links perception to action within the coordination dynamics theory. A primary assumption of the coordination dynamics approach is that environmental information is meaningful only in terms of the behavior it modifies. Across a series of single limb tasks and bimanual tasks it is shown that the relative motion and relative phase between limbs and joints is picked up through visual processes and supports observational learning of motor skills. Moreover, internal estimations of motor skill proficiency and competency are linked to the informational content found in relative motion and relative phase. Thus, the chapter links action to perception and vice versa and also links cognitive evaluations to the coordination dynamics that support action-perception and action-production processes.

Beyond the Examination Room

PubMed Central

O'Malley, Ann S; Forrest, Christopher B

2002-01-01

OBJECTIVE To assess whether primary care performance of low-income women's primary care delivery sites is associated with the strength of their relationships with their physicians. DESIGN Random-digit-dial and targeted household telephone survey of a population-based sample. SETTING Washington, D.C. census tracts with ≥30% of households below 200% of federal poverty threshold. PARTICIPANTS Women over age 40 (N = 1,205), 82% of whom were African American. MEASUREMENTS AND MAIN RESULTS The response rate was 85%. Primary care performance was assessed using women's ratings of their systems' accessibility (organizational, geographic, and financial), continuity, comprehensiveness, and coordination. Respondents' ratings of trust in their physicians, communication with their physicians, and compassion shown by their physicians were used to operationalize the patient-physician relationship. Controlling for population and insurance characteristics, 4 primary care features were positively associated with women's trust in and communication with their physicians: continuity with a single clinician, organizational accessibility of the practice, comprehensive care, and coordination of specialty care services. Better organizational access, but not geographic or financial access, was associated with greater levels of trust, compassion, and communication (odds ratios [ORs], 3.2, 7.4, and 6.9, respectively; P≤ .01). Women who rated highest their doctor's ability to take care of all of their health care needs (highest level of comprehensiveness) had 11 times the odds of trusting their physician (P≤ .01) and 6 times the odds of finding their physicians compassionate and communicative (P≤ .01), compared to those with the lowest level of comprehensiveness. CONCLUSIONS Primary care delivery sites organized to be more accessible, to link patients with the same clinician for their visits, to provide for all of a woman's health care needs, and to coordinate specialty care services are associated with stronger relationships between low-income women and their physicians. Primary care systems that fail to emphasize these features of primary care may jeopardize the clinician-patient relationship and indirectly the quality of care and health outcomes. PMID:11903777

"Here the Scientists Explain What I Said." Coordination Practices Elicited during the Enactment of the Results and Discussion Sections of Adapted Primary Literature

ERIC Educational Resources Information Center

Falk, Hedda; Yarden, Anat

2009-01-01

Adapted primary literature (APL) is a novel text genre that retains the authentic characteristics of primary literature. Learning through APL represents an educational intervention with an authentic scientific context. In this case study, we analyzed the 80-min discourse developed during the enactment of an article from an APL-based curriculum in…

Patients' experiences in different models of community health centers in southern China.

PubMed

Wang, Harry H X; Wong, Samuel Y S; Wong, Martin C S; Wei, Xiao Lin; Wang, Jia Ji; Li, Donald K T; Tang, Jin Ling; Gao, Gemma Y; Griffiths, Sian M

2013-01-01

Current health care reforms in China have an overall goal of strengthening primary care through the establishment and expansion of primary care networks based on community health centers (CHCs). Implementation in urban areas has led to the emergence of different models of ownership and management. The objective of this study was to evaluate the primary care experiences of patients in the Pearl River Delta as measured by the Primary Care Assessment Tool (PCAT) and the relationships with ownership and management in the 3 different models we describe. This cross-sectional study was conducted on-site at CHCs in 3 cities within the Pearl River Delta, China, using a multistage cluster sampling method. A validated Mandarin Chinese version of the PCAT-Adult Edition (short version) was adopted to collect information from adult patients regarding their experiences with primary care sources. PCAT scores for individual primary care attributes and total primary care assessment scores were assessed with respect to sociodemographic characteristics, health characteristics, and health care service utilization across 3 primary care models. One thousand four hundred forty (1,440) primary care patients responded to the survey, for an overall response rate of 86.1%. Respondents gave government-owned and -managed CHCs the highest overall PCAT scores when compared with CHCs either managed by hospitals (95.18 vs 90.81; P = .005) or owned by private and social entities (95.18 vs 90.69; P =.007) as a result of better first-contact care (better first-contact utilization) and coordination of care (better service coordination and information system). Factors that were positively and significantly associated with higher overall assessment scores included the presence of a chronic condition (P <.001), having medical insurance (P = .006), and a self-reported good health status (P <.001). This study suggests that government-owned and -managed CHCs may be able to provide better first-contact care in terms of utilization and coordination of care, and may be better at solving the problem of underutilization of the CHCs as the first-contact point of care, one key problem facing the reforms in China.

A snapshot of the organization and provision of primary care in Turkey

PubMed Central

2011-01-01

Background This WHO study aimed to support Turkey in its efforts to strengthen the primary care (PC) system by implementing the WHO Primary Care Evaluation Tool (PCET). This article provides an overview of the organization and provision of primary care in Turkey. Methods The WHO Primary Care Evaluation Tool was implemented in two provinces (Bolu and Eskişehir) in Turkey in 2007/08. The Tool consists of three parts: a national questionnaire concerning the organisation and financing of primary care; a questionnaire for family doctors; and a questionnaire for patients who visit a family health centre. Results Primary care has just recently become an official health policy priority with the introduction of a family medicine scheme. Although the supply of family doctors (FDs) has improved, they are geographically uneven distributed, and nationwide shortages of primary care staff remain. Coordination of care could be improved and quality control mechanisms were lacking. However, patients were very satisfied with the treatment by FDs. Conclusions The study provides an overview of the current state of PC in Turkey for two provinces with newly introduced family medicine, by using a structured approach to evaluate the essential functions of PC, including governance, financing, resource generation, as well as the characteristics of a "good" service delivery system (as being accessible, comprehensive, coordinated and continuous). PMID:21542904

A Teaching Hospital Medical Clinic: Secondary Rather than Primary Care.

ERIC Educational Resources Information Center

Fletcher, Suzanne; And Others

1979-01-01

A review of 287 patient visits to a teaching hospital polyclinic shows that most patients had multiple problems that required the help of subspecialists. However, the patients' needs for accessibility, comprehensiveness, coordination, and continuity are as great as those of patients receiving primary care. Implications for academic internal…

76 FR 33768 - Agency Information Collection Activities; Proposed Collection: Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-09

... the application may be obtained through the appropriate State Primary Care Offices, State Primary Care..., and by supporting their efforts to build better systems of care. The NHSC Site Application, which.... Dated: June 6, 2011. Reva Harris, Acting Director, Division of Policy and Information Coordination. [FR...

Young "Science Ambassadors" Raise the Profile of Science

ERIC Educational Resources Information Center

Ridley, Katie

2014-01-01

Katie Ridley, science coordinator at St. Gregory's Catholic Primary School, Liverpool, UK, states that the inspiration for "science ambassadors" came after embarking on the Primary Science Quality Mark programme at their school. Ridley realized that science was just not recognised as such by the children, they talked about scientific…

47 CFR 97.519 - Coordinating examination sessions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... qualified examinees, forward electronically all required data to the FCC. All data forwarded must be... itself or under the supervision of a VEC or VEs designated by the FCC; or (3) Cancel the operator/primary... instancce of such cancellation, the person will be granted an operator/primary station license consistent...

[Coordination between pharmaceutical services for integrated pharmacotherapy: the case of Catalonia].

PubMed

Costa, Karen Sarmento; Goldbaum, Moisés; Guayta-Escolies, Rafel; Modamio, Pilar; Mariño, Eduardo Luis; Tolsá, José Luis Segú

2017-08-01

Pharmaceutical policies have been considered strategies to contribute to the guarantee of care coordination and clinical integration. This study sought to describe the pharmaceutical services developed at different levels of care in the health network in Catalonia, as well as to identify and analyze the mechanisms and instruments that act as facilitators and/or barriers to the coordination of pharmacotherapy. This is a descriptive study of 12 cases of hospital pharmacy services, primary care and community pharmacies. Advances related to the perception, formalization and clinical and assistance coordination of the pharmaceutical services were identified. However, weaknesses and potential improvements in coordination were observed. The conclusion drawn was that the different tools and instruments implemented appear to facilitate a greater possibility of integration between pharmaceutical services and the latter with the health services network to contribute to integrated pharmacotherapy.

Bringing Wellness to Schools: Opportunities for and Challenges to Mental Health Integration in School-Based Health Centers.

PubMed

Lai, Karen; Guo, Sisi; Ijadi-Maghsoodi, Roya; Puffer, Maryjane; Kataoka, Sheryl H

2016-12-01

School-based health centers (SBHCs) reduce access barriers to mental health care and improve educational outcomes for youths. This qualitative study evaluated the innovations and challenges of a unique network of SBHCs in a large, urban school district as the centers attempted to integrate health, mental health, and educational services. The 43 participants sampled included mental health providers, primary care providers, and care coordinators at 14 SBHCs. Semistructured interviews with each participant were audio recorded and transcribed. Themes were identified and coded by using Atlas.ti 5.1 and collapsed into three domains: operations, partnership, and engagement. Interviews revealed provider models ranging from single agencies offering both primary care and mental health services to colocated services. Sites where the health agency provided at least some mental health services reported more mental health screenings. Many sites used SBHC wellness coordinators and coordination team meetings to facilitate relationships between schools and health agency and community mental health clinic providers. Partnership challenges included confidentiality policies and staff turnover. Participants also highlighted student and parent engagement through culturally sensitive services, peer health advocates, and "drop-in" lunches. Staffing and operational models are critical in the success of integrating primary care, mental health care, and education. Among the provider models observed, the combined primary care and mental health provider model offered the most integrated services. Despite barriers, providers and schools have begun to implement novel solutions to operational problems and family engagement in mental health services.

From Exclusion to Inclusion; Supporting Special Educational Needs Co-Ordinators to Keep Children in Mainstream Education: A Qualitative Psychoanalytic Research Project

ERIC Educational Resources Information Center

Evans, Angela

2013-01-01

This paper draws on my doctoral research study based on consulting work with three primary school Special Educational Needs Co-ordinators (SENCos) that took place in 2008. The study examined the interactions that arose in the consultations with the SENCos and their staff. The findings that emerged from the application of Grounded Theory research…

Patients' experience of Chinese Medicine Primary Care Services: Implications on Improving Coordination and Continuity of Care.

PubMed

Chung, Vincent Ch; Yip, Benjamin Hk; Griffiths, Sian M; Yu, Ellen Lm; Liu, Siya; Ho, Robin St; Wu, Xinyin; Leung, Albert Wn; Sit, Regina Ws; Wu, Justin Cy; Wong, Samuel Ys

2015-12-21

Chinese medicine (CM) is major form of traditional and complementary medicine used by Chinese populations. Evaluation on patients' experience on CM service is essential for improving service quality. This cross sectional study aims (i) to assess how CM clinics with different administrative model differ in terms of quality from patients' perspective; and (ii) to investigate how quality varies with patients' demographic and health characteristics. Five hundred and sixteen patients were sampled from charity and semi-public CM clinics in Hong Kong, and were invited to assess their experience using the Primary Care Assessment Tool (PCAT). Results indicated that overall mean PCAT scoring is satisfactory, achieving 70.7% (91.26/129) of total score. Ratings were lower in areas of "coordination of patient information", "continuity of care", and "range of service provided". Impact of administrative models, including involvement of tax-funded healthcare system and outreach delivery, were minimal after adjusting for patient characteristics. Demographic and health characteristics of patients did not contribute to substantial variations in scoring. To improve patient experience, policy makers should consider strengthening care coordination, continuity and comprehensiveness in CM primary care services. Sharing of electronic records and establishing referral system are potential solutions for linking CM and conventional healthcare services.

After-hours access to primary care practices linked with lower emergency department use and less unmet medical need.

PubMed

O'Malley, Ann S

2013-01-01

One goal of the Affordable Care Act is to improve patients' access to primary care and the coordination of that care. An important ingredient in achieving that goal is ensuring that patients have access to their primary care practice outside of regular business hours. This analysis of the 2010 Health Tracking Household Survey found that among people with a usual source of primary care, 40.2 percent reported that their practice offered extended hours, such as at night or on weekends. The analysis also found that one in five people who attempted after-hours contact with their primary care provider reported it was "very difficult" or "somewhat difficult" to reach a clinician. Those who reported less difficulty contacting a clinician after hours had significantly fewer emergency department visits (30.4 percent compared to 37.7 percent) and lower rates of unmet medical need (6.1 percent compared to 13.7 percent) than people who experienced more difficulty. The findings provide a valuable baseline on after-hours access, especially as patient-centered medical homes and accountable care organizations expand. Increasing support to primary care practices to offer or coordinate after-hours care may help reduce rates of emergency department use and unmet medical need.

Interprofessional Communication Patterns During Patient Discharges: A Social Network Analysis.

PubMed

Pinelli, Vincent A; Papp, Klara K; Gonzalo, Jed D

2015-09-01

Optimal care delivery requires timely, efficient, and accurate communication among numerous providers and their patients, especially during hospital discharge. Little is known about communication patterns during this process. Our aim was to assess the frequency and patterns of communication between patients and providers during patient discharges from a hospital-based medicine unit. On the day of the patient's discharge, the patient and all healthcare providers involved in the discharge were interviewed using structured questions related to information exchange during the discharge process. Each interview identified the frequency and method of communication between participants, including synchronous (e.g., face-to-face) and asynchronous (e.g., through electronic medical record) routes. Communication patterns were visually diagramed using social network analysis. Forty-six patients were screened for inclusion in the network analysis. Of those, seven patients who were fully oriented and able to complete an interview and all providers who participated in their care during the discharge were selected for inclusion in the analysis. In all, 72 healthcare professionals contributing to the discharge process were interviewed, including physicians, nurses, therapists, pharmacists, care coordinators, social workers, and nutritionists. Patients' mean age was 63, length-of-stay was 7.8 days, and most (86 %) were discharged to home. On average, 11 roles were involved with each discharge. The majority of communication was synchronous (562 events vs. 469 asynchronous events, p = 0.004). Most communication events occurred between the primary nurse and patient and the care coordinator and primary nurse (mean 3.9 and 2.3 events/discharge, respectively). Participants identified intern physicians as most important in the discharge process, followed by primary nurses and care coordinators. In patients being discharged from the medicine service, communication was more frequently synchronous, and occurred between intern physicians, primary nurses, and patients. Potential improvements in coordinating patients' discharges are possible by reorganizing systems to optimize efficient communication.

Primary care and care for older persons: position paper of the European Forum for Primary Care.

PubMed

Boeckxstaens, Pauline; De Graaf, Pim

2011-01-01

This article explores how to address the needs of the growing number of older patients in primary care practice. Primary care is not a fixed organisational structure but a combination of functional characteristics which has developed variably in European countries with differing responses to the emerging needs of older persons. Multimorbidity, frailty, disability and dependence play out differently in older persons; a key challenge for primary care is to provide a response that is adapted to the needs of individuals - as they see them and not as the professional defines them. Indeed, growing experience shows how to involve older persons in taking decisions. Contrary to popular opinion, older persons often rate their quality of life as high. Indeed, comprehensive primary care offers health promotion and prevention: also older people may benefit from measures that support their health and independence and some case descriptions show this potential. Although most people prefer to be in their own environment (home, community) during the last stage of life, providing end-of-life care in the community is a challenge for primary care because it requires continuity and coordination with specialist care. Successful models of care however do exist. Delivering seamless integrated care to older persons is a central theme in primary care. Rather than disease management, in primary care, case management is the preferred approach. Proactive geriatric assessment of individual medical, functional and social needs, including loneliness and isolation, has been shown to be useful and its place in primary care is the subject of further research. Clinical practice guidelines for multimorbidity are badly needed. Non-adherence to medication, linked to multiple and uncoordinated prescriptions, is a widespread and costly problem. Successful approaches in primary care are being developed, including the use of electronic patient files. With the general practitioner (GP) as the central care provider, primary care is increasingly teamwork, and the role of nurses and other (new) professions in primary care is developing constantly. The composition and coordination of teams are two components of one of the major complexities to address: how to provide individualised care with standardisation at organisation the level. (Lack of) Coordination with specialist care remains a widespread problem and needs attention from policy makers and practitioners alike. Alignment with home care and social services remains a challenge in all countries, not least because of the different funding arrangements between the services. Further priorities for research and development are summarised.

A failure to communicate: a qualitative exploration of care coordination between hospitalists and primary care providers around patient hospitalizations.

PubMed

Jones, Christine D; Vu, Maihan B; O'Donnell, Christopher M; Anderson, Mary E; Patel, Snehal; Wald, Heidi L; Coleman, Eric A; DeWalt, Darren A

2015-04-01

Care coordination between adult hospitalists and primary care providers (PCPs) is a critical component of successful transitions of care from hospital to home, yet one that is not well understood. The purpose of this study was to understand the challenges in coordination of care, as well as potential solutions, from the perspective of hospitalists and PCPs in North Carolina. We conducted an exploratory qualitative study with 58 clinicians in four hospitalist focus groups (n = 32), three PCP focus groups (n = 19), and one hybrid group with both hospitalists and PCPs (n = 7). Interview guides included questions about care coordination, information exchange, follow-up care, accountability, and medication management. Focus group sessions were recorded, transcribed verbatim, and analyzed in ATLAS.ti. The constant comparative method was used to evaluate differences between hospitalists and PCPs. Hospitalists and PCPs were found to encounter similar care coordination challenges, including (1) lack of time, (2) difficulty reaching other clinicians, (3) lack of personal relationships with other clinicians, (4) lack of information feedback loops, (5) medication list discrepancies, and (6) lack of clarity regarding accountability for pending tests and home health. Hospitalists additionally noted difficulty obtaining timely follow-up appointments for after-hours or weekend discharges. PCPs additionally noted (1) not knowing when patients were hospitalized, (2) not having hospital records for post-hospitalization appointments, (3) difficulty locating important information in discharge summaries, and (4) feeling undervalued when hospitalists made medication changes without involving PCPs. Hospitalists and PCPs identified common themes of successful care coordination as (1) greater efforts to coordinate care for "high-risk" patients, (2) improved direct telephone access to each other, (3) improved information exchange through shared electronic medical records, (4) enhanced interpersonal relationships, and (5) clearly defined accountability. Hospitalists and PCPs encounter similar challenges in care coordination, yet have important experiential differences related to sending and receiving roles for hospital discharges. Efforts to improve coordination of care between hospitalists and PCPs should aim to understand perspectives of clinicians in each setting.

76 FR 48171 - Agency Information Collection Activities: Proposed Collection: Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-08

... through the appropriate State Primary Care Offices, State Primary Care Associations and the NHSC. The... to build better systems of care. The NHSC Site Application, which renames and revises the previous... Director, Division of Policy and Information Coordination. [FR Doc. 2011-20077 Filed 8-5-11; 8:45 am...

Finding Inquiry in Discourses of Audit and Reform in Primary Schools

ERIC Educational Resources Information Center

Williams, Julian; Corbin, Brian; McNamara, Olwen

2007-01-01

In this paper we examine the discourses of Primary school numeracy coordinators responsible for auditing, monitoring and supporting their colleagues in relation to the introduction and embedding of the National Numeracy Strategy (NNS) in the UK. Cultural-Historical Activity Theory (CHAT) focuses our analysis on the contradictory coupling of…

Towards a New Generation: A Primary Prevention Plan for New Jersey. A Report.

ERIC Educational Resources Information Center

New Jersey Governor's Juvenile Justice and Delinquency Prevention Advisory Committee, Trenton, NJ.

The New Jersey Juvenile Justice and Delinquency Prevention Advisory Committee and its Prevention Subcommittee have developed an interagency plan to promote primary prevention activities statewide. The plan identifies the initial steps which must be undertaken by major sectors of the community to begin to effectively coordinate activities and…

75 FR 29677 - PLMR Licensing; Frequency Coordination and Eligibility Issues

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-27

... in the portions of the 1427-1432 MHz band where non- medical telemetry has primary status. We take... free of harmful interference. The band 1427-1432 MHz is shared between medical and non-medical telemetry operations. Generally, WMTS has primary status in the lower half of the band, and non-medical...

Utilisation and Satisfaction with Rehabilitation Services in Children with Primary Language Impairment Transitioning to School: Parents' Perspective

ERIC Educational Resources Information Center

Mazer, Barbara; Dion, Karyne; Moryoussef, Aguy

2017-01-01

Children with disabilities require coordinated services to optimise transition into school. This study compared type, frequency and approach to service utilisation for children with primary language impairment transitioning from rehabilitation to the educational system, and examined parent satisfaction. Parents responded to a telephone…

Organization of Model Systems for Primary Care Practice and Education: Problems and Issues

ERIC Educational Resources Information Center

Seidel, Henry M.

1975-01-01

Lists issues in planning primary care education, e.g. fear of dilution of excellence, competition for resources, delivery of care, the teaching objective, M.D. and new health professional, benefit and service structure, financial structure, physical and administrative locus, marketing. Emphasis is on coordination of educational research, and…

Sensory Flask Cells in Sponge Larvae Regulate Metamorphosis via Calcium Signaling.

PubMed

Nakanishi, Nagayasu; Stoupin, Daniel; Degnan, Sandie M; Degnan, Bernard M

2015-12-01

The Porifera (sponges) is one of the earliest phyletic lineages to branch off the metazoan tree. Although the body-plan of sponges is among the simplest in the animal kingdom and sponges lack nervous systems that communicate environmental signals to other cells, their larvae have sensory systems that generate coordinated responses to environmental cues. In eumetazoans (Cnidaria and Bilateria), the nervous systems of larvae often regulate metamorphosis through Ca(2+)-dependent signal transduction. In sponges, neither the identity of the receptor system that detects an inductive environmental cue (hereafter "metamorphic cues") nor the signaling system that mediates settlement and metamorphosis are known. Using a combination of behavioral assays and surgical manipulations, we show here that specialized epithelial cells-referred to as flask cells-enriched in the anterior third of the Amphimedon queenslandica larva are most likely to be the sensory cells that detect the metamorphic cues. Surgical removal of the region enriched in flask cells in a larva inhibits the initiation of metamorphosis. The flask cell has an apical sensory apparatus with a cilium surrounded by an apical F-actin-rich protrusion, and numerous vesicles, hallmarks of eumetazoan sensory-neurosecretory cells. We demonstrate that these flask cells respond to metamorphic cues by elevating intracellular Ca(2+) levels, and that this elevation is necessary for the initiation of metamorphosis. Taken together, these analyses suggest that sponge larvae have sensory-secretory epithelial cells capable of converting exogenous cues into internal signals via Ca(2+)-mediated signaling, which is necessary for the initiation of metamorphosis. Similarities in the morphology, physiology, and function of the sensory flask cells in sponge larvae with the sensory/neurosecretory cells in eumetazoan larvae suggest this sensory system predates the divergence of Porifera and Eumetazoa. © The Author 2015. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

Linking clinician interaction and coordination to clinical performance in Patient-Aligned Care Teams.

PubMed

Hysong, Sylvia J; Thomas, Candice L; Spitzmüller, Christiane; Amspoker, Amber B; Woodard, LeChauncy; Modi, Varsha; Naik, Aanand D

2016-01-15

Team coordination within clinical care settings is a critical component of effective patient care. Less is known about the extent, effectiveness, and impact of coordination activities among professionals within VA Patient-Aligned Care Teams (PACTs). This study will address these gaps by describing the specific, fundamental tasks and practices involved in PACT coordination, their impact on performance measures, and the role of coordination task complexity. First, we will use a web-based survey of coordination practices among 1600 PACTs in the national VHA. Survey findings will characterize PACT coordination practices and assess their association with clinical performance measures. Functional job analysis, using 6-8 subject matter experts who are 3rd and 4th year residents in VA Primary Care rotations, will be utilized to identify the tasks involved in completing clinical performance measures to standard. From this, expert ratings of coordination complexity will be used to determine the level of coordinative complexity required for each of the clinical performance measures drawn from the VA External Peer Review Program (EPRP). For objective 3, data collected from the first two methods will evaluate the effect of clinical complexity on the relationships between measures of PACT coordination and their ratings on the clinical performance measures. Results from this study will support successful implementation of coordinated team-based work in clinical settings by providing knowledge regarding which aspects of care require the most complex levels of coordination and how specific coordination practices impact clinical performance.

Voluntary coordination as a strategy of plan implementation for health systems agencies.

PubMed

Berry, D E; Candia, G R

1979-10-01

Health planning agencies are faced with the difficult mission of guiding change within a large complex social system whose power is dispersed. Initial short- and long-range plans have been established as frameworks, and now the major focus is implementation. Regulation (non-voluntary coordination) and voluntary coordination are the major means of implementation. Voluntary coordination is a significant strategy for consideration by Health Systems Agencies (HSAs). It may interact with regulation as a competitor, substitute, or complement. Because of limited regulatory powers, HSAs are dependent upon voluntary coordination as a major means of influencing behavior. Conflict, a major feature of voluntary coordination, has the potential of being used as a constructive means for dialogue; negotiation and bargaining may become positive approaches to arriving at decisions. Legitimized community authority is the primary source of authority in a strategy dominated by voluntary coordination as contrasted to state or federal mandates in a regulatory strategy. Knowledge of the environment within which the HSA operates will assist HSA staff and board to arrive at rational and realistic decisions.

Non-neural ectoderm is really neural: evolution of developmental patterning mechanisms in the non-neural ectoderm of chordates and the problem of sensory cell homologies.

PubMed

Holland, Linda Z

2005-07-15

In chordates, the ectoderm is divided into the neuroectoderm and the so-called non-neural ectoderm. In spite of its name, however, the non-neural ectoderm contains numerous sensory cells. Therefore, the term "non-neural" ectoderm should be replaced by "general ectoderm." At least in amphioxus and tunicates and possibly in vertebrates as well, both the neuroectoderm and the general ectoderm are patterned anterior/posteriorly by mechanisms involving retinoic acid and Hox genes. In amphioxus and tunicates the ectodermal sensory cells, which have a wide range of ciliary and microvillar configurations, are mostly primary neurons sending axons to the CNS, although a minority lack axons. In contrast, vertebrate mechanosensory cells, called hair cells, are all secondary neurons that lack axons and have a characteristic eccentric cilium adjacent to a group of microvilli of graded lengths. It has been highly controversial whether the ectodermal sensory cells in the oral siphons of adult tunicates are homologous to vertebrate hair cells. In some species of tunicates, these cells appear to be secondary neurons, and microvillar and ciliary configurations of some of these cells approach those of vertebrate hair cells. However, none of the tunicate cells has all the characteristics of a hair cell, and there is a high degree of variation among ectodermal sensory cells within and between different species. Thus, similarities between the ectodermal sensory cells of any one species of tunicate and craniate hair cells may well represent convergent evolution rather than homology. Copyright 2005 Wiley-Liss, Inc.

A novel ICK mutation causes ciliary disruption and lethal endocrine-cerebro-osteodysplasia syndrome.

PubMed

Oud, Machteld M; Bonnard, Carine; Mans, Dorus A; Altunoglu, Umut; Tohari, Sumanty; Ng, Alvin Yu Jin; Eskin, Ascia; Lee, Hane; Rupar, C Anthony; de Wagenaar, Nathalie P; Wu, Ka Man; Lahiry, Piya; Pazour, Gregory J; Nelson, Stanley F; Hegele, Robert A; Roepman, Ronald; Kayserili, Hülya; Venkatesh, Byrappa; Siu, Victoria M; Reversade, Bruno; Arts, Heleen H

2016-01-01

Endocrine-cerebro-osteodysplasia (ECO) syndrome [MIM:612651] caused by a recessive mutation (p.R272Q) in Intestinal cell kinase (ICK) shows significant clinical overlap with ciliary disorders. Similarities are strongest between ECO syndrome, the Majewski and Mohr-Majewski short-rib thoracic dysplasia (SRTD) with polydactyly syndromes, and hydrolethalus syndrome. In this study, we present a novel homozygous ICK mutation in a fetus with ECO syndrome and compare the effect of this mutation with the previously reported ICK variant on ciliogenesis and cilium morphology. Through homozygosity mapping and whole-exome sequencing, we identified a second variant (c.358G > T; p.G120C) in ICK in a Turkish fetus presenting with ECO syndrome. In vitro studies of wild-type and mutant mRFP-ICK (p.G120C and p.R272Q) revealed that, in contrast to the wild-type protein that localizes along the ciliary axoneme and/or is present in the ciliary base, mutant proteins rather enrich in the ciliary tip. In addition, immunocytochemistry revealed a decreased number of cilia in ICK p.R272Q-affected cells. Through identification of a novel ICK mutation, we confirm that disruption of ICK causes ECO syndrome, which clinically overlaps with the spectrum of ciliopathies. Expression of ICK-mutated proteins result in an abnormal ciliary localization compared to wild-type protein. Primary fibroblasts derived from an individual with ECO syndrome display ciliogenesis defects. In aggregate, our findings are consistent with recent reports that show that ICK regulates ciliary biology in vitro and in mice, confirming that ECO syndrome is a severe ciliopathy.

Targeted Therapies for Autosomal Dominant Polycystic Kidney Disease.

PubMed

Stayner, Cherie; Brooke, Darby G; Bates, Michael; Eccles, Michael R

2018-05-07

Autosomal dominant polycystic kidney disease (ADPKD) is the most common life-threatening genetic disease in humans, affecting approximately 1 in 500 people. ADPKD is characterized by cyst growth in the kidney leading to progressive parenchymal damage and is the underlying pathology in approximately 10% of patients requiring hemodialysis or transplantation for end-stage kidney disease. The two proteins that are mutated in ADPKD, polycystin-1 and polycystin-2, form a complex located on the primary cilium and the plasma membrane to facilitate calcium ion release in the cell. There is currently no Food and Drug Administration (FDA)-approved therapy to cure or slow the progression of the disease. Rodent ADPKD models do not completely mimic the human disease, and therefore preclinical results have not always successfully translated to the clinic. Moreover, the toxicity of many of these potential therapies has led to patient withdrawals from clinical trials. Here, we review compounds in a clinical trial for treating ADPKD, and we examine the feasibility of using a kidney-targeted approach, with potential for broadening the therapeutic window, decreasing treatment-associated toxicity and increasing the efficacy of agents that have demonstrated activity in animal models. We make recommendations for integrating kidney-targeted therapies with current treatment regimes, to achieve a combined approach to treating ADPKD. Many compounds are currently in clinical trial for ADPKD, yet to date, none are FDA-approved for treating this disease. Patients could benefit from efficacious pharmacotherapy, especially if it can be kidney-targeted, and intensive efforts continue to be focused on this goal. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

"In Our Corner": A Qualitative Descriptive Study of Patient Engagement in a Community-Based Care Coordination Program.

PubMed

Sefcik, Justine S; Petrovsky, Darina; Streur, Megan; Toles, Mark; O'Connor, Melissa; Ulrich, Connie M; Marcantonio, Sherry; Coburn, Ken; Naylor, Mary D; Moriarty, Helene

2018-03-01

The purpose of this study was to explore participants' experience in the Health Quality Partners (HQP) Care Coordination Program that contributed to their continued engagement. Older adults with multiple chronic conditions often have limited engagement in health care services and face fragmented health care delivery. This can lead to increased risk for disability, mortality, poor quality of life, and increased health care utilization. A qualitative descriptive design with two focus groups was conducted with a total of 20 older adults enrolled in HQP's Care Coordination Program. Conventional content analysis was the analytical technique. The overarching theme resulting from the analysis was "in our corner," with subthemes "opportunities to learn and socialize" and "dedicated nurses," suggesting that these are the primary contributing factors to engagement in HQP's Care Coordination Program. Study findings suggest that nurses play an integral role in patient engagement among older adults enrolled in a care coordination program.

Safety-net providers in some US communities have increasingly embraced coordinated care models.

PubMed

Cunningham, Peter; Felland, Laurie; Stark, Lucy

2012-08-01

Safety-net organizations, which provide health services to uninsured and low-income people, increasingly are looking for ways to coordinate services among providers to improve access to and quality of care and to reduce costs. In this analysis, a part of the Community Tracking Study, we examined trends in safety-net coordination activities from 2000 to 2010 within twelve communities in the United States and found a notable increase in such activities. Six of the twelve communities had made formal efforts to link uninsured people to medical homes and coordinate care with specialists in 2010, compared to only two communities in 2000. We also identified key attributes of safety-net coordinated care systems, such as reliance on a medical home for meeting patients' primary care needs, and lingering challenges to safety-net integration, such as competition among hospitals and community health centers for Medicaid patients.

"Are We Being De-Gifted, Miss?" Primary School Gifted and Talented Co-Ordinators' Responses to the Gifted and Talented Education Policy in England

ERIC Educational Resources Information Center

Koshy, Valsa; Pinheiro-Torres, Catrin

2013-01-01

Over a decade ago the UK government launched its gifted and talented education policy in England, yet there has been very little published research which considers how schools and teachers are interpreting and implementing the policy. By seeking the views of the gifted and talented co-ordinators (For ease of reference, the term gifted and talented…

Estimates of point defect production in α-quartz using molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Cowen, Benjamin J.; El-Genk, Mohamed S.

2017-07-01

Molecular dynamics (MD) simulations are performed to investigate the production of point defects in α-quartz by oxygen and silicon primary knock-on atoms (PKAs) of 0.25-2 keV. The Wigner-Seitz (WS) defect analysis is used to identify the produced vacancies, interstitials, and antisites, and the coordination defect analysis is used to identify the under and over-coordinated oxygen and silicon atoms. The defects at the end of the ballistic phase and the residual defects, after annealing, increase with increased PKA energy, and are statistically the same for the oxygen and silicon PKAs. The WS defect analysis results show that the numbers of the oxygen vacancies and interstitials (VO, Oi) at the end of the ballistic phase is the highest, followed closely by those of the silicon vacancies and interstitials (VSi, Sii). The number of the residual oxygen and silicon vacancies and interstitials are statistically the same. In addition, the under-coordinated OI and SiIII, which are the primary defects during the ballistic phase, have high annealing efficiencies (>89%). The over-coordinated defects of OIII and SiV, which are not nearly as abundant in the ballistic phase, have much lower annealing efficiencies (<63%) that decrease with increased PKA energy.

A heart failure initiative to reduce the length of stay and readmission rates.

PubMed

White, Sabrina Marie; Hill, Alethea

2014-01-01

The purpose of this pilot was to improve multidisciplinary coordination of care and patient education and foster self-management behaviors. The primary and secondary outcomes achieved from this pilot were to decrease the 30-day readmission rate and heart failure length of stay. The primary practice site was an inpatient medical-surgical nursing unit. The length of stay decreased from 6.05% to 4.42% for heart failure diagnostic-related group 291 as a result of utilizing the model. The length of stay decreased from 3.9% to 3.09%, which was also less than the national rate of 3.8036% for diagnostic-related group 292. In addition, the readmission rate decreased from 23.1% prior to January 2013 to 12.9%. Implementation of standards of care coordination can decrease length of stay, readmission rate, and improve self-management. Implementation of evidence-based heart failure guidelines, improved interdisciplinary coordination of care, patient education, self-management skills, and transitional care at the time of discharge improved overall heart failure outcome measures. Utilizing the longitudinal model of care to transition patients to home aided in evaluating social support, resource allocation and utilization, access to care postdischarge, and interdisciplinary coordination of care. The collaboration between disciplines improved continuity of care, patient compliance to their discharge regimen, and adequate discharge follow-up.

Supporting Medical Home Transformation Through Evaluation of Patient Experience in a Large Culturally Diverse Primary Care Safety Net.

PubMed

Cook, Nicole; Hollar, T Lucas; Zunker, Christie; Peterson, Michael; Phillips, Teina; De Lucca, Michael

2016-01-01

The prevalence of chronic disease in the United States is rapidly increasing, with a disproportionate number of underserved, vulnerable patients sharing the burden. The Patient-Centered Medical Home (PCMH) is a care delivery model that has shown promise to improve primary care and address the burden of chronic illness. The purpose of this study was to (1) understand patient characteristics that might influence perceived patient experience in a large primary care safety net undergoing PCMH transformation; (2) identify community-level quality improvement opportunities to support ongoing transformation activities; and (3) establish a baseline of patient experience across the primary care safety net that could be used in repeated evaluations over the course of transformation. A cross-sectional study design was used to conduct this research. A total of 351 racially and ethnically diverse patients of 4 primary care safety net organizations in Broward County, Florida, were surveyed regarding their experience with access to care and coordination of care. Reported access to care and coordination of care. Patients with chronic disease who reported having visited the clinic 3 or more times in the past 12 months reported a better coordination of care experience than patients who had fewer than 3 visits in the past 12 months (odds ratio = 3.57; 95% confidence interval, 1.76-7.24). Patients without chronic disease who had been receiving care at the clinic for 2 or more years of care reported worse experience with access to care than patients with less than 2 years of care (odds ratio = 0.26; 95% confidence interval, 0.11-0.60.) Race, ethnicity, language, and education were not significant predictors of patient experience. Findings support ongoing efforts to improve patient engagement among all patients and to enhance resources to manage chronic disease, including community-based self-management programs, in primary care safety nets undergoing PCMH transformation.

Ultrastructural observation on ‘transitional tubules’ in human oviductal ciliogenic cells

PubMed Central

HAGIWARA, HARUO; AOKI, TAKEO; FUJIMOTO, TOYOSHI

1997-01-01

In the human oviduct epithelium during ciliogenesis, short tubular structures were found in the transitional zone between the basal body and cilium. The tubules, termed transitional tubules from their location, were 34–36 nm in diameter and 0.13±0.06 μm in length; the number around a basal body was variable, but usually 4–6. The cytoplasmic leaflets of the tubule membranes were coated by electron-dense material and appeared to be connected to alar sheets. The transitional tubules existed transiently during ciliogenesis. The exact role of transitional tubules is unknown, but considering their location, they may fix the basal body in the apical cytoplasm during ciliary elongation and/or may be related to formation of alar sheets. PMID:9306204

Hearing in Insects.

PubMed

Göpfert, Martin C; Hennig, R Matthias

2016-01-01

Insect hearing has independently evolved multiple times in the context of intraspecific communication and predator detection by transforming proprioceptive organs into ears. Research over the past decade, ranging from the biophysics of sound reception to molecular aspects of auditory transduction to the neuronal mechanisms of auditory signal processing, has greatly advanced our understanding of how insects hear. Apart from evolutionary innovations that seem unique to insect hearing, parallels between insect and vertebrate auditory systems have been uncovered, and the auditory sensory cells of insects and vertebrates turned out to be evolutionarily related. This review summarizes our current understanding of insect hearing. It also discusses recent advances in insect auditory research, which have put forward insect auditory systems for studying biological aspects that extend beyond hearing, such as cilium function, neuronal signal computation, and sensory system evolution.

Metachronal wave of artificial cilia array actuated by applied magnetic field

NASA Astrophysics Data System (ADS)

Tsumori, Fujio; Marume, Ryuma; Saijou, Akinori; Kudo, Kentaro; Osada, Toshiko; Miura, Hideshi

2016-06-01

In this paper, a biomimetic microstructure related to cilia, which are effective fluidic and conveying systems in nature, is described. Authors have already reported that a magnetic elastomer pillar actuated by a rotating magnetic field can work like a natural cilium. In the present work, we show examples of a cilia array with a metachronal wave as the next step. A metachronal wave is a sequential action of a number of cilia. It is theoretically known that a metachronal wave gives a higher fluidic efficiency; however, there has been no report on a metachronal wave by artificial cilia. We prepared magnetic elastomer pillars that contain chainlike clusters of magnetic particles. The orientation of chains was set to be different in each pillar so that each pillar will deform with a different phase.

Comparing Quality of Public Primary Care between Hong Kong and Shanghai Using Validated Patient Assessment Tools

PubMed Central

Wei, Xiaolin; Li, Haitao; Yang, Nan; Wong, Samuel Y. S.; Owolabi, Onikepe; Xu, Jianguang; Shi, Leiyu; Tang, Jinling; Li, Donald; Griffiths, Sian M.

2015-01-01

Objectives Primary care is the key element of health reform in China. The objective of this study was to compare patient assessed quality of public primary care between Hong Kong, a city with established primary care environment influenced by its colonial history, and Shanghai, a city leading primary care reform in Mainland China; and to measure the equity of care in the two cities. Methods Cross sectional stratified random sampling surveys were conducted in 2011. Data were collected from 1,994 respondents in Hong Kong and 811 respondents in Shanghai. A validated Chinese version of the primary care assessment tool was employed to assess perceived quality of primary care with respect to socioeconomic characteristics and health status. Results We analyzed 391 and 725 respondents in Hong Kong and Shanghai, respectively, who were regular public primary care users. Respondents in Hong Kong reported significant lower scores in first contact accessibility (1.59 vs. 2.15), continuity of care (2.33 vs. 3.10), coordination of information (2.84 vs. 3.64), comprehensiveness service availability (2.43 vs. 3.31), comprehensiveness service provided (2.11 vs. 2.40), and the total score (23.40 vs. 27.40), but higher scores in first contact utilization (3.15 vs. 2.54) and coordination of services (2.67 vs. 2.40) when compared with those in Shanghai. Respondents with higher income reported a significantly higher total primary care score in Hong Kong, but not in Shanghai. Conclusions Respondents in Shanghai reported better quality of public primary care than those in Hong Kong, while quality of public primary care tended to be more equitable in Shanghai. PMID:25826616

Senior Information Officials Standard

EPA Pesticide Factsheets

This document establishes the (SIOs) as the Environmental Protection Agency’s (EPA) primary points of accountability for the effective oversight, coordination, and management of information and information technology (IT)

Primary data collection in health technology assessment.

PubMed

McIsaac, Michelle L; Goeree, Ron; Brophy, James M

2007-01-01

This study discusses the value of primary data collection as part of health technology assessment (HTA). Primary data collection can help reduce uncertainty in HTA and better inform evidence-based decision making. However, methodological issues such as choosing appropriate study design and practical concerns such as the value of collecting additional information need to be addressed. The authors emphasize the conditions required for successful primary data collection in HTA: experienced researchers, sufficient funding, and coordination among stakeholders, government, and researchers. The authors conclude that, under specific conditions, primary data collection is a worthwhile endeavor in the HTA process.

Care coordination for children with special needs in Medicaid: lessons from Medicare.

PubMed

Stewart, Kate A; Bradley, Katharine W V; Zickafoose, Joseph S; Hildrich, Rachel; Ireys, Henry T; Brown, Randall S

2018-04-01

To provide actionable recommendations for improving care coordination programs for children with special healthcare needs (CSHCN) in Medicaid managed care.  Literature review and interviews with stakeholders and policy experts to adapt lessons learned from Medicare care coordination programs for CSHCN in Medicaid managed care. We reviewed syntheses of research on Medicare care coordination programs to identify lessons learned from successful programs. We adapted findings from Medicare to CSHCN in Medicaid based on an environmental scan and discussions with experts. The scan focused on Medicaid financing and eligibility for care coordination and how these intersect with Medicaid managed care. The expert discussions included pediatricians, Medicaid policy experts, Medicaid medical directors, and a former managed care executive, all experienced in care coordination for CSHCN. We found 6 elements that are consistently associated with improved outcomes from Medicare care coordination programs and relevant to CSHCN in Medicaid: 1) identifying and targeting high-risk patients, 2) clearly articulating what outcomes programs are likely to improve, 3) encouraging active engagement between care coordinators and primary care providers, 4) requiring some in-person contact between care coordinators and patients, 5) facilitating information sharing among providers, and 6) supplementing care coordinators' expertise with that of other clinical experts. States and Medicaid managed care organizations have many options for designing effective care coordination programs for CSHCN. Their choices should account for the diversity of conditions among CSHCN, families' capacity to coordinate care, and social determinants of health.

The Oral Health Care Manager in a Patient-Centered Health Facility.

PubMed

Theile, Cheryl Westphal; Strauss, Shiela M; Northridge, Mary Evelyn; Birenz, Shirley

2016-06-01

The dental hygienist team member has an opportunity to coordinate care within an interprofessional practice as an oral health care manager. Although dental hygienists are currently practicing within interprofessional teams in settings such as pediatric offices, hospitals, nursing homes, schools, and federally qualified health centers, they often still assume traditional responsibilities rather than practicing to the full extent of their training and licenses. This article explains the opportunity for the dental hygiene professional to embrace patient-centered care as an oral health care manager who can facilitate integration of oral and primary care in a variety of health care settings. Based on an innovative model of collaboration between a college of dentistry and a college of nursing, an idea emerged among several faculty members for a new management method for realizing continuity and coordination of comprehensive patient care. Involved faculty members began working on the development of an approach to interprofessional practice with the dental hygienist serving as an oral health care manager who would address both oral health care and a patient's related primary care issues through appropriate referrals and follow-up. This approach is explained in this article, along with the results of several pilot studies that begin to evaluate the feasibility of a dental hygienist as an oral health care manager. A health care provider with management skills and leadership qualities is required to coordinate the interprofessional provision of comprehensive health care. The dental hygienist has the opportunity to lead closer integration of oral and primary care as an oral health care manager, by coordinating the team of providers needed to implement comprehensive, patient-centered care. Copyright © 2016 Elsevier Inc. All rights reserved.

A genetic signature of the evolution of loss of flight in the Galapagos cormorant

USGS Publications Warehouse

Burga, Alejandro; Wang, Weiguang; Ben-David, Eyal; Wolf, Paul C.; Ramey, Andy M.; Verdugo, Claudio; Lyons, Karen; Parker, Patricia G.; Kruglyak, Leonid

2017-01-01

INTRODUCTIONChanges in the size and proportion of limbs and other structures have played a key role in the evolution of species. One common class of limb modification is recurrent wing reduction and loss of flight in birds. Indeed, Darwin used the occurrence of flightless birds as an argument in favor of his theory of natural selection. Loss of flight has evolved repeatedly and is found among 26 families of birds in 17 different orders. Despite the frequency of these modifications, we have a limited understanding of their underpinnings at the genetic and molecular levels.RATIONALETo better understand the evolution of changes in limb size, we studied a classic case of recent loss of flight in the Galapagos cormorant (Phalacrocorax harrisi). Cormorants are large water birds that live in coastal areas or near lakes, and P. harrisi is the only flightless cormorant among approximately 40 extant species. The entire population is distributed along the coastlines of Isabela and Fernandina islands in the Galapagos archipelago. P. harrisi has a pair of short wings, which are smaller than those of any other cormorant. The extreme reduction of the wings and pectoral skeleton observed in P. harrisi is an attractive model for studying the evolution of loss of flight because it occurred very recently; phylogenetic evidence suggests that P. harrisi diverged from its flighted relatives within the past 2 million years. We developed a comparative and predictive genomics approach that uses the genome sequences of P. harrisi and its flighted relatives to find candidate genetic variants that likely contributed to the evolution of loss of flight.RESULTSWe sequenced and de novo assembled the whole genomes of P. harrisi and three closely related flighted cormorant species. We identified thousands of coding variants exclusive to P. harrisi and classified them according to their probability of altering protein function based on conservation. Variants most likely to alter protein function were significantly enriched in genes mutated in human skeletal ciliopathies, including Ofd1, Evc, Wdr34, and Ift122. We carried out experiments in Caenorhabditis elegans to confirm that a missense variant present in the Galapagos cormorant IFT122 protein is sufficient to affect ciliary function. The primary cilium is essential for Hedgehog (Hh) signaling in vertebrates, and individuals affected by ciliopathies have small limbs and ribcages, mirroring the phenotype of P. harrisi. We also identified a 4–amino acid deletion in the regulatory domain of Cux1, a highly conserved transcription factor that has been experimentally shown to regulate limb growth in chicken. The four missing amino acids are perfectly conserved in all birds and mammals sequenced to date. We tested the consequences of this deletion in a chondrogenic cell line and showed that it impairs the ability of CUX1 to transcriptionally up-regulate cilia-related genes (some of which contain function-altering variants in P. harrisi) and to promote chondrogenic differentiation. Finally, we show that positive selection may have played a role in the fixation of the variants associated with loss of flight in P. harrisi.CONCLUSIONOur results indicate that the combined effect of variants in genes necessary for the correct transcriptional regulation and function of the primary cilium likely contributed to the evolution of highly reduced wings and other skeletal adaptations associated with loss of flight in P. harrisi. Our approach may be generally useful for identification of variants underlying evolutionary novelty from genomes of closely related species.

Examining Primary Schools' Physical Education Coordinators' Pedagogical Content Knowledge of Games: Are We Just Playing as This?

ERIC Educational Resources Information Center

Ward, Gavin

2013-01-01

A detailed insight into how the current educational climate influences the pedagogical decisions made by primary school teachers when teaching games is limited. Studies examining the pedagogical content knowledge (PCK) of teachers within physical education have revealed its close relationship with specific forms of subject knowledge. In…

Using TAPS Focused Assessments as Part of Our Teacher Assessment Approach

ERIC Educational Resources Information Center

Barber, Kerry-Anne

2018-01-01

As the Science Co-ordinator at St Paul's RC Primary School, the author has been involved in producing and trialling resources for the Teacher Assessment in Primary Science (TAPS) project over the last four years. This article explains how St Paul's has used the Focused Assessments (FAs). The author has always tried to promote enquiry-based…

75 FR 19277 - PLMR Licensing; Frequency Coordination and Eligibility Issues

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-14

... band (1427-1429.5 MHz), and non-medical telemetry in the upper half of the band (1429.5-1432 MHz). Non... secondary basis on those portions of the 1427-1432 MHz shared band where non-medical telemetry is primary...-medical telemetry has primary status. Some WMTS operations in the portions of the 1427-1432 MHz band where...

The phagotrophic origin of eukaryotes and phylogenetic classification of Protozoa.

PubMed

Cavalier-Smith, T

2002-03-01

Eukaryotes and archaebacteria form the clade neomura and are sisters, as shown decisively by genes fragmented only in archaebacteria and by many sequence trees. This sisterhood refutes all theories that eukaryotes originated by merging an archaebacterium and an alpha-proteobacterium, which also fail to account for numerous features shared specifically by eukaryotes and actinobacteria. I revise the phagotrophy theory of eukaryote origins by arguing that the essentially autogenous origins of most eukaryotic cell properties (phagotrophy, endomembrane system including peroxisomes, cytoskeleton, nucleus, mitosis and sex) partially overlapped and were synergistic with the symbiogenetic origin of mitochondria from an alpha-proteobacterium. These radical innovations occurred in a derivative of the neomuran common ancestor, which itself had evolved immediately prior to the divergence of eukaryotes and archaebacteria by drastic alterations to its eubacterial ancestor, an actinobacterial posibacterium able to make sterols, by replacing murein peptidoglycan by N-linked glycoproteins and a multitude of other shared neomuran novelties. The conversion of the rigid neomuran wall into a flexible surface coat and the associated origin of phagotrophy were instrumental in the evolution of the endomembrane system, cytoskeleton, nuclear organization and division and sexual life-cycles. Cilia evolved not by symbiogenesis but by autogenous specialization of the cytoskeleton. I argue that the ancestral eukaryote was uniciliate with a single centriole (unikont) and a simple centrosomal cone of microtubules, as in the aerobic amoebozoan zooflagellate Phalansterium. I infer the root of the eukaryote tree at the divergence between opisthokonts (animals, Choanozoa, fungi) with a single posterior cilium and all other eukaryotes, designated 'anterokonts' because of the ancestral presence of an anterior cilium. Anterokonts comprise the Amoebozoa, which may be ancestrally unikont, and a vast ancestrally biciliate clade, named 'bikonts'. The apparently conflicting rRNA and protein trees can be reconciled with each other and this ultrastructural interpretation if long-branch distortions, some mechanistically explicable, are allowed for. Bikonts comprise two groups: corticoflagellates, with a younger anterior cilium, no centrosomal cone and ancestrally a semi-rigid cell cortex with a microtubular band on either side of the posterior mature centriole; and Rhizaria [a new infrakingdom comprising Cercozoa (now including Ascetosporea classis nov.), Retaria phylum nov., Heliozoa and Apusozoa phylum nov.], having a centrosomal cone or radiating microtubules and two microtubular roots and a soft surface, frequently with reticulopodia. Corticoflagellates comprise photokaryotes (Plantae and chromalveolates, both ancestrally with cortical alveoli) and Excavata (a new protozoan infrakingdom comprising Loukozoa, Discicristata and Archezoa, ancestrally with three microtubular roots). All basal eukaryotic radiations were of mitochondrial aerobes; hydrogenosomes evolved polyphyletically from mitochondria long afterwards, the persistence of their double envelope long after their genomes disappeared being a striking instance of membrane heredity. I discuss the relationship between the 13 protozoan phyla recognized here and revise higher protozoan classification by updating as subkingdoms Lankester's 1878 division of Protozoa into Corticata (Excavata, Alveolata; with prominent cortical microtubules and ancestrally localized cytostome--the Parabasalia probably secondarily internalized the cytoskeleton) and Gymnomyxa [infrakingdoms Sarcomastigota (Choanozoa, Amoebozoa) and Rhizaria; both ancestrally with a non-cortical cytoskeleton of radiating singlet microtubules and a relatively soft cell surface with diffused feeding]. As the eukaryote root almost certainly lies within Gymnomyxa, probably among the Sarcomastigota, Corticata are derived. Following the single symbiogenetic origin of chloroplasts in a corticoflagellate host with cortical alveoli, this ancestral plant radiated rapidly into glaucophytes, green plants and red algae. Secondary symbiogeneses subsequently transferred plastids laterally into different hosts, making yet more complex cell chimaeras--probably only thrice: from a red alga to the corticoflagellate ancestor of chromalveolates (Chromista plus Alveolata), from green algae to a secondarily uniciliate cercozoan to form chlorarachneans and independently to a biciliate excavate to yield photosynthetic euglenoids. Tertiary symbiogenesis involving eukaryotic algal symbionts replaced peridinin-containing plastids in two or three dinoflagellate lineages, but yielded no major novel groups. The origin and well-resolved primary bifurcation of eukaryotes probably occurred in the Cryogenian Period, about 850 million years ago, much more recently than suggested by unwarranted backward extrapolations of molecular 'clocks' or dubious interpretations as 'eukaryotic' of earlier large microbial fossils or still more ancient steranes. The origin of chloroplasts and the symbiogenetic incorporation of a red alga into a corticoflagellate to create chromalveolates may both have occurred in a big bang after the Varangerian snowball Earth melted about 580 million years ago, thereby stimulating the ensuing Cambrian explosion of animals and protists in the form of simultaneous, poorly resolved opisthokont and anterokont radiations.

Ambulatory elderly patients of primary care physicians: functional, psychosocial and environmental predictors of need for social work care management.

PubMed

Berkman, B; Shearer, S; Simmons, W J; White, M; Robinson, M; Sampson, S; Holmes, W; Allison, D; Thomson, J A

1996-01-01

With increasing numbers of elderly people, and the escalating costs of health care, screening becomes increasingly important for identifying those older people with social health care needs who appear in their primary care physicians' offices. Many people are not aware of available social services. Families with serious social problems are not finding the help they need. The aim of this study was to develop and refine a questionnaire as a screening tool to identify elderly outpatients in primary care settings who are at high risk for psychological, social or environmental needs. This study identified those ten factors at each site which were most indicative that further intervention was needed. There were consistencies among the coordinators across sites in terms of what factors triggered intervention. Activities of Daily Living (ADLs) and Instrumental Activities of Daily Living (IADLs) were more likely to be predictive of the coordinator's intervention than were other factors.

[Management of heart failure in cardiology and primary care (MICCAP) program: Improving the management of patients with heart failure].

PubMed

Barrios, V; Escobar, C; Pallares, V; Egocheaga, M I; Lobos, J M; Bover, R; Gómez Doblas, J J; Cosín, J

2018-03-26

Despite current treatments, morbidity and mortality of patients with heart failure remain high. The late diagnosis of heart failure, the insufficient heart failure treatment (i.e. not using the appropriate drugs, prescribing lower doses of drugs than recommended, etc.), and a poor coordination between different health care levels, may explain, at least in part, these figures. The Management of Heart Failure in Cardiology and Primary Care (MICCAP) program has been developed with the aim of optimising the integrated management of patients with heart failure between Primary Care and Cardiology, through the improvement of coordination between both health care levels. This includes continuous medical education to reinforce the diagnostic and therapeutic skills of general practitioners in the field of heart failure. The rationale and objectives of the MICCAP program are summarised in this article. Copyright © 2018 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

The Mayor's Influence in Urban School Desegregation

ERIC Educational Resources Information Center

Dunaway, David King; Beckum, Leonard Charles

1977-01-01

There are five primary areas in which mayors exert visible and invisible influence--appointments, decision-making, public statements, coordination of resources, and provision of basic services. (Author/IRT)

Potential access to primary health care: what does the National Program for Access and Quality Improvement data show?

PubMed Central

Uchôa, Severina Alice da Costa; Arcêncio, Ricardo Alexandre; Fronteira, Inês Santos Estevinho; Coêlho, Ardigleusa Alves; Martiniano, Claudia Santos; Brandão, Isabel Cristina Araújo; Yamamura, Mellina; Maroto, Renata Melo

2016-01-01

Objective: to analyze the influence of contextual indicators on the performance of municipalities regarding potential access to primary health care in Brazil and to discuss the contribution from nurses working on this access. Method: a multicenter descriptive study based on secondary data from External Evaluation of the National Program for Access and Quality Improvement in Primary Care, with the participation of 17,202 primary care teams. The chi-square test of proportions was used to verify differences between the municipalities stratified based on size of the coverage area, supply, coordination, and integration; when necessary, the chi-square test with Yates correction or Fisher's exact test were employed. For the population variable, the Kruskal-Wallis test was used. Results: the majority of participants were nurses (n=15.876; 92,3%). Statistically significant differences were observed between the municipalities in terms of territory (p=0.0000), availability (p=0.0000), coordination of care (p=0.0000), integration (p=0.0000) and supply (p=0.0000), verifying that the municipalities that make up area 6 tend to have better performance in these dimensions. Conclusion: areas 4,5 and 6 performed better in every analyzed dimension, and the nurse had a leading role in the potential to access primary health care in Brazil. PMID:26959332

A systematic review of the care coordination measurement landscape

PubMed Central

2013-01-01

Background Care coordination has increasingly been recognized as an important aspect of high-quality health care delivery. Robust measures of coordination processes will be essential tools to evaluate, guide and support efforts to understand and improve coordination, yet little agreement exists among stakeholders about how to best measure care coordination. We aimed to review and characterize existing measures of care coordination processes and identify areas of high and low density to guide future measure development. Methods We conducted a systematic review of measures published in MEDLINE through April 2012 and identified from additional key sources and informants. We characterized included measures with respect to the aspects of coordination measured (domain), measurement perspective (patient/family, health care professional, system representative), applicable settings and patient populations (by age and condition), and data used (survey, chart review, administrative claims). Results Among the 96 included measure instruments, most relied on survey methods (88%) and measured aspects of communication (93%), in particular the transfer of information (81%). Few measured changing coordination needs (11%). Nearly half (49%) of instruments mapped to the patient/family perspective; 29% to the system representative and 27% to the health care professionals perspective. Few instruments were applicable to settings other than primary care (58%), inpatient facilities (25%), and outpatient specialty care (22%). Conclusions New measures are needed that evaluate changing coordination needs, coordination as perceived by health care professionals, coordination in the home health setting, and for patients at the end of life. PMID:23537350

Genotet: An Interactive Web-based Visual Exploration Framework to Support Validation of Gene Regulatory Networks.

PubMed

Yu, Bowen; Doraiswamy, Harish; Chen, Xi; Miraldi, Emily; Arrieta-Ortiz, Mario Luis; Hafemeister, Christoph; Madar, Aviv; Bonneau, Richard; Silva, Cláudio T

2014-12-01

Elucidation of transcriptional regulatory networks (TRNs) is a fundamental goal in biology, and one of the most important components of TRNs are transcription factors (TFs), proteins that specifically bind to gene promoter and enhancer regions to alter target gene expression patterns. Advances in genomic technologies as well as advances in computational biology have led to multiple large regulatory network models (directed networks) each with a large corpus of supporting data and gene-annotation. There are multiple possible biological motivations for exploring large regulatory network models, including: validating TF-target gene relationships, figuring out co-regulation patterns, and exploring the coordination of cell processes in response to changes in cell state or environment. Here we focus on queries aimed at validating regulatory network models, and on coordinating visualization of primary data and directed weighted gene regulatory networks. The large size of both the network models and the primary data can make such coordinated queries cumbersome with existing tools and, in particular, inhibits the sharing of results between collaborators. In this work, we develop and demonstrate a web-based framework for coordinating visualization and exploration of expression data (RNA-seq, microarray), network models and gene-binding data (ChIP-seq). Using specialized data structures and multiple coordinated views, we design an efficient querying model to support interactive analysis of the data. Finally, we show the effectiveness of our framework through case studies for the mouse immune system (a dataset focused on a subset of key cellular functions) and a model bacteria (a small genome with high data-completeness).

'It's not therapy, it's gardening': community gardens as sites of comprehensive primary healthcare.

PubMed

Marsh, Pauline; Brennan, Sebrina; Vandenberg, Miriam

2018-05-28

Using a participatory research framework, researchers at the Centre for Rural Health, University of Tasmania, explored the potential of Community Gardens to function as comprehensive primary healthcare (CPHC) environments. Community gardeners, coordinators, volunteers and Neighbourhood House coordinators discussed their understandings of the health benefits of community gardens, how they contribute to broad CPHC aims and the barriers and enablers to greater CPHC contributions in the future. This research identifies therapeutic features of Community Gardens and explores the correlations between these and CPHC. It is concluded that there are strong synergies between the aims and activities of Community Gardens and CPHC. To augment the therapeutic capacity of these sites requires adequate resourcing and skill development, suitable design, funding and policy support, along with innovative partnerships with health professionals.

Teleform scannable data entry: an efficient method to update a community-based medical record? Community care coordination network Database Group.

PubMed Central

Guerette, P.; Robinson, B.; Moran, W. P.; Messick, C.; Wright, M.; Wofford, J.; Velez, R.

1995-01-01

Community-based multi-disciplinary care of chronically ill individuals frequently requires the efforts of several agencies and organizations. The Community Care Coordination Network (CCCN) is an effort to establish a community-based clinical database and electronic communication system to facilitate the exchange of pertinent patient data among primary care, community-based and hospital-based providers. In developing a primary care based electronic record, a method is needed to update records from the field or remote sites and agencies and yet maintain data quality. Scannable data entry with fixed fields, optical character recognition and verification was compared to traditional keyboard data entry to determine the relative efficiency of each method in updating the CCCN database. PMID:8563414

Primary separation between three aircraft using traffic displays

NASA Technical Reports Server (NTRS)

Chappell, S. L.; Palmer, E. A.

1983-01-01

The use of a sophisticated traffic and map display termed electronic flight rules (EFR) by general aviation pilots for primary seperation in low density airspace is studied. The experimental flights were made under four conditions: with and without sensor noise in the traffic information and with and without communications for traffic coordination. Pilots were required to maintain two miles horizontal and 500 ft vertical separation from other aircraft for 24 different traffic situations repeated randomly for each of the four experimental conditions. Of 1152 aircraft encounters 12.8 percent were in violation of separation minimums. In general, the effects of sensor noise were minimal, communications affected some of the measures, and the group effect was quite significant. When pilots were able to communicate and coordinate their maneuvers, the time to resolve conflict was reduced.

Education and occupational status in 14 countries: the role of educational institutions and labour market coordination.

PubMed

Andersen, Robert; van de Werfhorst, Herman G

2010-06-01

This article explores the role of national institutional factors--more specifically, the level of skill transparency of the education system and labour market coordination--in accounting for cross-national differences in the relationship between education and occupational status. Consistent with previous research, our findings suggest that skill transparency is the primary moderator. Countries with a highly transparent educational system (i.e., extensive tracking, strong vocational orientation, limited tertiary enrolment) tend to be characterized by a strong relationship between education and occupational status. These findings hold even after controlling for the level of labour market coordination. Nevertheless, we also find that labour market coordination plays an independent role by dampening the effect of education on occupational status. Taken together, these results suggest two quite different policy implications: (1) strengthening the skill transparency of the education system by increasing secondary and tertiary-level differentiation may strengthen the relationship between education and occupation, regardless of the level of coordination, and (2) increasing labour market coordination could lead to improved social inclusion and a reduction in inequalities related to educational attainment.

Kinematic properties of the helicopter in coordinated turns

NASA Technical Reports Server (NTRS)

Chen, R. T. N.; Jeske, J. A.

1981-01-01

A study on the kinematic relationship of the variables of helicopter motion in steady, coordinated turns involving inherent sideslip is described. A set of exact kinematic equations which govern a steady coordinated helical turn about an Earth referenced vertical axis is developed. A precise definition for the load factor parameter that best characterizes a coordinated turn is proposed. Formulas are developed which relate the aircraft angular rates and pitch and roll attitudes to the turn parameters, angle of attack, and inherent sideslip. A steep, coordinated helical turn at extreme angles of attack with inherent sideslip is of primary interest. The bank angle of the aircraft can differ markedly from the tilt angle of the normal load factor. The normal load factor can also differ substantially from the accelerometer reading along the vertical body axis of the aircraft. Sideslip has a strong influence on the pitch attitude and roll rate of the helicopter. Pitch rate is independent of angle of attack in a coordinated turn and in the absence of sideslip, angular rates about the stability axes are independent of the aerodynamic characteristics of the aircraft.

Using social media to assess care coordination goals and plans for leukemia patients and survivors.

PubMed

Strekalova, Yulia A; Hawkins, Kimberly E; Drusbosky, Leylah M; Cogle, Cristopher R

2018-05-23

Care coordination has been shown to have a positive effect on the management of chronic disease. Specific to the management of leukemia, coordination may occur between primary care physician, medical and radiation oncologists, surgeons, cardiologists, and genetics specialists. Experiencing gaps in communication and care coordination, many health consumers seek instrumental support in their social circles, including online forums and networks. The goal of this theory-guided study was to provide an in-depth assessment of how individuals use online forums to deliberate about their goals and plans for leukemia care coordination. Guided by the planning theory of communication, the data were collected from the American Cancer Society Cancer Survivors Network and included 125 original posts and 1,248 responses. Thematic analysis and axial coding were applied to analyze the data. Goal-related themes included overcoming the diffusion of care coordination and achieving health management cohesion. Planning themes included social health management, communication self-efficacy, and role deliberation. Online patient forums provide an interactive platform for patients and caregivers to engage in active conversations, which in turn can serve as identifiers of care coordination needs. Communication with those who share similar experiences allows cancer patients and survivors to accumulate functional health literacy, gain communication self-efficacy, and articulate a care coordination role acceptable to them.

Survey Instruments to Assess Patient Experiences With Access and Coordination Across Health Care Settings: Available and Needed Measures.

PubMed

Quinn, Martha; Robinson, Claire; Forman, Jane; Krein, Sarah L; Rosland, Ann-Marie

2017-07-01

Improving access can increase the providers a patient sees, and cause coordination challenges. For initiatives that increase care across health care settings, measuring patient experiences with access and care coordination will be crucial. Map existing survey measures of patient experiences with access and care coordination expected to be relevant to patients accessing care across settings. Preliminarily examine whether aspects of access and care coordination important to patients are represented by existing measures. Structured literature review of domains and existing survey measures related to access and care coordination across settings. Survey measures, and preliminary themes from semistructured interviews of 10 patients offered VA-purchased Community Care, were mapped to identified domains. We identified 31 existing survey instruments with 279 items representing 6 access and 5 care coordination domains relevant to cross-system care. Domains frequently assessed by existing measures included follow-up coordination, primary care access, cross-setting coordination, and continuity. Preliminary issues identified in interviews, but not commonly assessed by existing measures included: (1) acceptability of distance to care site given patient's clinical situation; (2) burden on patients to access and coordinate care and billing; (3) provider familiarity with Veteran culture and VA processes. Existing survey instruments assess many aspects of patient experiences with access and care coordination in cross-system care. Systems assessing cross-system care should consider whether patient surveys accurately reflect the level of patients' concerns with burden to access and coordinate care, and adequately reflect the impact of clinical severity and cultural familiarity on patient preferences.

The Continuing Development of Primary Sector Physical Education: Working Together to Raise Quality of Provision

ERIC Educational Resources Information Center

Sloan, Stephen

2010-01-01

This paper sets out to provide further insight as to the reasons why many schools within the primary sector continue to find it difficult to ensure quality provision for physical education (PE) and school sport. It examines why class teachers, including the subject coordinator, possess concerns about teaching PE. It asks the question of who is…

Articulating a Deficit Perspective: A Survey of the Attitudes of Post-Primary English Language Support Teachers and Coordinators

ERIC Educational Resources Information Center

Lyons, Zachary

2010-01-01

Issues related to supporting the language of schooling have become important social and educational policy concerns in Ireland. This article reports on a three-year investigation of the micro-climate of English language support provision in 70 post-primary schools since 2007 and highlights potential points of leverage in the educational system for…

The SENCO Role in Post-Primary Schools in Ireland: Victims or Agents of Change?

ERIC Educational Resources Information Center

Fitzgerald, Johanna; Radford, Julie

2017-01-01

This paper considers the role of Special Educational Needs Coordinators (SENCOs) in mainstream post-primary schools (12-18 years) in Ireland. Little is known of the role in the Irish context and it is hoped that this research will inform policy. The Irish educational landscape has witnessed seismic change recently with further transformation…

Oncologists' perspectives on post-cancer treatment communication and care coordination with primary care physicians.

PubMed

Klabunde, C N; Haggstrom, D; Kahn, K L; Gray, S W; Kim, B; Liu, B; Eisenstein, J; Keating, N L

2017-07-01

Post-treatment cancer care is often fragmented and of suboptimal quality. We explored factors that may affect cancer survivors' post-treatment care coordination, including oncologists' use of electronic technologies such as e-mail and integrated electronic health records (EHRs) to communicate with primary care physicians (PCPs). We used data from a survey (357 respondents; participation rate 52.9%) conducted in 2012-2013 among medical oncologists caring for patients in a large US study of cancer care delivery and outcomes. Oncologists reported their frequency and mode of communication with PCPs, and role in providing post-treatment care. Seventy-five per cent said that they directly communicated with PCPs about post-treatment status and care recommendations for all/most patients. Among those directly communicating with PCPs, 70% always/usually used written correspondence, while 36% always/usually used integrated EHRs; telephone and e-mail were less used. Eighty per cent reported co-managing with PCPs at least one post-treatment general medical care need. In multivariate-adjusted analyses, neither communication mode nor intensity were associated with co-managing survivors' care. Oncologists' reliance on written correspondence to communicate with PCPs may be a barrier to care coordination. We discuss new research directions for enhancing communication and care coordination between oncologists and PCPs, and to better meet the needs of cancer survivors post-treatment. © 2017 John Wiley & Sons Ltd.

Operational and Functional Description of the AERA Packages,

DTIC Science & Technology

1983-09-11

implications: * Very early coordination with the pilot may be effected, to allow the pilot to resolve the problem (since he has primary responsibility for...but that this is a situation of which the controller and the pilot may want to be aware for planning purposes. 4.3.2.3 Controller’s Response The primary ...data link will be greatly expanded in AERA 2.01. The primary capability that affects the operation of t he ATC system is that non-control messages

Managing professionals: The emerging leadership role of Victorian Maternal and Child Health coordinators.

PubMed

Reiger, Kerreen; Keleher, Helen

2004-04-01

Drawing on research into cultural and organizational change in the Victorian Maternal and Child Health Service during the 1990s, this paper examines implications for the nursing leadership provided by service coordinators. The project included a quantitative survey of nurses and semistructured interviews with managers and coordinators. Under a strongly neo-liberal state government in Victoria, Australia, services were fundamentally restructured through tendering processes. A competitive, productivist culture was introduced that challenged the professional ethos of nurses and a primary health orientation to the care of mothers and infants. This paper focuses on the pressures that the entrepreneurial environment presented to maternal and child health nurses' identity and collegial relations and to the coordination role. It argues that coordinators emerged as a significant nursing management group at the interface of administrative change and the management of professional practice. Although many nurses skillfully negotiated tensions with peers and management, their leadership role needs further clarification and support.

The Physiologic Development of Speech Motor Control: Lip and Jaw Coordination

PubMed Central

Green, Jordan R.; Moore, Christopher A.; Higashikawa, Masahiko; Steeve, Roger W.

2010-01-01

This investigation was designed to describe the development of lip and jaw coordination during speech and to evaluate the potential influence of speech motor development on phonologic development. Productions of syllables containing bilabial consonants were observed from speakers in four age groups (i.e., 1-year-olds, 2-year-olds, 6-year-olds, and young adults). A video-based movement tracking system was used to transduce movement of the upper lip, lower lip, and jaw. The coordinative organization of these articulatory gestures was shown to change dramatically during the first several years of life and to continue to undergo refinement past age 6. The present results are consistent with three primary phases in the development of lip and jaw coordination for speech: integration, differentiation, and refinement. Each of these developmental processes entails the existence of distinct coordinative constraints on early articulatory movement. It is suggested that these constraints will have predictable consequences for the sequence of phonologic development. PMID:10668666

Increased identification of the primary care provider as the main source of asthma care among urban minority children.

PubMed

Iqbal, Sabah F; Jiggetts, Jennifer; Silverbrook, Cheryl; Shelef, Deborah Q; McCarter, Robert; Teach, Stephen J

2016-11-01

Urban, minority, and disadvantaged youth with asthma frequently use emergency departments (EDs) for episodic asthma care instead of their primary care providers (PCPs). We sought to increase the rate of guardians' identification of the PCP as the source of asthma care for their children through integrated electronic health records and care coordination. In this prospective cohort study, we implemented an electronic communication process between an asthma specialty clinic and PCPs coupled with short-term care coordination in sample of youth aged 2-12 years with asthma and surveyed their guardians at baseline and 3 and 6 months after the intervention. Guardians of 50 children (median age 5.8 years, 64% male, 98% African American, 94% public insurance) were enrolled. Compared to baseline, at 3 and 6 months after the intervention, significantly more guardians reported that the PCP was their child's primary asthma health care provider [70% at baseline, 85% at 3 months, 83% at 6 months (time averaged adjusted OR 77.4, 95% CI 3.0, 2027.1]. Further, significantly more guardians reported that they took their child to the PCP when the child experienced problems with his/her asthma [16% at baseline, 35% at 3 months, 41% at 6 months (time averaged adjusted odds ratio (OR) 10.6, 95% CI 2.7, 41.7]. Care in a subspecialty asthma clinic augmented by electronic communication with PCPs and short term care coordination was associated with significantly improved identification of PCPs as the primary source of asthma care in a cohort of urban minority youth.

Care coordination experiences of people with disabilities enrolled in medicaid managed care.

PubMed

Bowers, Anne; Owen, Randall; Heller, Tamar

2017-10-01

To understand the impact of experience and contacts with care coordinators on Medicaid Managed Care (MMC) enrollees with disabilities. Primary data was collected from a random sample of 6000 out of the 100,000 people with disabilities enrolled in one state's mandatory MMC program. Surveys were conducted through the mail, telephone, and Internet; 1041 surveys were completed. The sample used for analysis included 442 MMC enrollees who received care coordination. Regression analyses were conducted with the outcomes of number of unmet health care needs and enrollee appraisal of the health services they received. Race, age, gender, and disability variables controlled for demographic differences, and the independent variables included enrollee experience with a care coordinator (coordinator knowledge of enrollee medical history and whether the coordinator took into account enrollee wishes and input) and frequency of contact with a care coordinator. Positive enrollee experiences with care coordinators significantly related to more positive enrollee health service appraisals and fewer unmet health care needs; frequency of contact did not have any significant impacts. People with mental health disabilities and intellectual/developmental disabilities had significantly lower health service appraisals. People with mental health disabilities had significantly more unmet needs. Quality of care coordination, but not frequency of contact alone, is associated with better health outcomes for MMC enrollees. Implications for rehabilitation Care coordination is a core component of managed care and facilitates effective healthcare management for people with complex chronic conditions and disabilities. Better experiences with care coordinators is related to fewer unmet healthcare needs and more positive health care service appraisals for Medicaid managed care enrollees. The continuous development of person-centered care coordination strategies and training programs emphasizing quality relationships between coordinators and consumers should be prioritized.

A narrative synthesis of the impact of primary health care delivery models for refugees in resettlement countries on access, quality and coordination.

PubMed

Joshi, Chandni; Russell, Grant; Cheng, I-Hao; Kay, Margaret; Pottie, Kevin; Alston, Margaret; Smith, Mitchell; Chan, Bibiana; Vasi, Shiva; Lo, Winston; Wahidi, Sayed Shukrullah; Harris, Mark F

2013-11-07

Refugees have many complex health care needs which should be addressed by the primary health care services, both on their arrival in resettlement countries and in their transition to long-term care. The aim of this narrative synthesis is to identify the components of primary health care service delivery models for such populations which have been effective in improving access, quality and coordination of care. A systematic review of the literature, including published systematic reviews, was undertaken. Studies between 1990 and 2011 were identified by searching Medline, CINAHL, EMBASE, Cochrane Library, Scopus, Australian Public Affairs Information Service - Health, Health and Society Database, Multicultural Australian and Immigration Studies and Google Scholar. A limited snowballing search of the reference lists of all included studies was also undertaken. A stakeholder advisory committee and international advisers provided papers from grey literature. Only English language studies of evaluated primary health care models of care for refugees in developed countries of resettlement were included. Twenty-five studies met the inclusion criteria for this review of which 15 were Australian and 10 overseas models. These could be categorised into six themes: service context, clinical model, workforce capacity, cost to clients, health and non-health services. Access was improved by multidisciplinary staff, use of interpreters and bilingual staff, no-cost or low-cost services, outreach services, free transport to and from appointments, longer clinic opening hours, patient advocacy, and use of gender-concordant providers. These services were affordable, appropriate and acceptable to the target groups. Coordination between the different health care services and services responding to the social needs of clients was improved through case management by specialist workers. Quality of care was improved by training in cultural sensitivity and appropriate use of interpreters. The elements of models most frequently associated with improved access, coordination and quality of care were case management, use of specialist refugee health workers, interpreters and bilingual staff. These findings have implications for workforce planning and training.

A narrative synthesis of the impact of primary health care delivery models for refugees in resettlement countries on access, quality and coordination

PubMed Central

2013-01-01

Introduction Refugees have many complex health care needs which should be addressed by the primary health care services, both on their arrival in resettlement countries and in their transition to long-term care. The aim of this narrative synthesis is to identify the components of primary health care service delivery models for such populations which have been effective in improving access, quality and coordination of care. Methods A systematic review of the literature, including published systematic reviews, was undertaken. Studies between 1990 and 2011 were identified by searching Medline, CINAHL, EMBASE, Cochrane Library, Scopus, Australian Public Affairs Information Service – Health, Health and Society Database, Multicultural Australian and Immigration Studies and Google Scholar. A limited snowballing search of the reference lists of all included studies was also undertaken. A stakeholder advisory committee and international advisers provided papers from grey literature. Only English language studies of evaluated primary health care models of care for refugees in developed countries of resettlement were included. Results Twenty-five studies met the inclusion criteria for this review of which 15 were Australian and 10 overseas models. These could be categorised into six themes: service context, clinical model, workforce capacity, cost to clients, health and non-health services. Access was improved by multidisciplinary staff, use of interpreters and bilingual staff, no-cost or low-cost services, outreach services, free transport to and from appointments, longer clinic opening hours, patient advocacy, and use of gender-concordant providers. These services were affordable, appropriate and acceptable to the target groups. Coordination between the different health care services and services responding to the social needs of clients was improved through case management by specialist workers. Quality of care was improved by training in cultural sensitivity and appropriate use of interpreters. Conclusion The elements of models most frequently associated with improved access, coordination and quality of care were case management, use of specialist refugee health workers, interpreters and bilingual staff. These findings have implications for workforce planning and training. PMID:24199588

Care coordination in PMAQ-AB: an Item Response Theory-based analysis.

PubMed

Souza, Miriam Francisco de; Santos, Alaneir de Fatima Dos; Reis, Ilka Afonso; Santos, Marcos Antônio da Cunha; Jorge, Alzira de Oliveira; Machado, Antônio Tomaz Gonzaga da Matta; Andrade, Eli Iola Gurgel; Cherchiglia, Mariangela Leal

2017-01-01

Analyze the quality of the National Program for Primary Care Access and Quality Improvement variables to evaluate the coordination of primary care. A cross-sectional study based on data from 17,202 primary care teams that participated in the National Program for Primary Care Access and Quality Improvement in 2012. Based on the Item Response Theory, Samejima's Gradual Response Model was used to estimate the score related to the level of coordination. The Cronbach's alpha and Spearman' coefficients and the point-biserial correlation were used to analyze the internal consistency and the correlation between the items and between the items and the total score. We evaluated the assumptions of unidimensionality and local independence of the items. Cloud-type word charts aided in the interpretation of coordination levels. The Program items with the greatest discrimination in coordination level were: telephone/Internet existence, institutional communication flows, and matrix support actions. The specialists' contact frequency with the primary care and integrated electronic medical record required a greater level of coordination among the teams. The Cronbach' alpha was 0.8018. The institutional communication flows and telephone/Internet items had a higher correlation with the total score. Coordination scores ranged from -2.67 (minimum) to 2.83 (maximum). More communication, information exchange, matrix support, health care in the territory and the domicile had a significant influence on the levels of coordination. The ability to provide information and the frequency of contact among professionals are important elements for a comprehensive, continuous and high-quality care. Analisar a qualidade das variáveis do Programa de Melhoria do Acesso e da Qualidade da Atenção Básica para avaliar a coordenação na atenção básica do cuidado. Estudo transversal baseado em dados de 17.202 equipes de atenção básica que participaram do Programa de Melhoria do Acesso e da Qualidade da Atenção Básica em 2012. Baseado na Teoria de Resposta ao Item, o Modelo de Resposta Gradual de Samejima foi utilizado para estimação do escore relacionado ao nível de coordenação. Os coeficientes alfa de Cronbach, Spearman e ponto bisserial foram utilizados para análise da consistência interna e da correlação entre os itens e de itens com o escore total. Foram avaliadas as suposições de unidimensionalidade e de independência local dos itens. Gráficos do tipo nuvem de palavras auxiliaram na interpretação dos níveis de coordenação. Os itens do Programa com maior discriminação do nível de coordenação foram: existência de telefone/internet, fluxos institucionais de comunicação e ações de apoio matricial. A frequência de contato de especialistas com a atenção básica e prontuário eletrônico integrado exigiram maior nível de coordenação das equipes. O coeficiente alfa de Cronbach total 0,8018. Os itens fluxos institucional de comunicação e telefone/internet tiveram maior correlação com o escore total. Os escores de coordenação variaram entre -2,67 (mínimo) e 2,83 (máximo). Maior grau de comunicação, troca de informações, apoio matricial, cuidado no território e domicílio tiveram peso relevante nos níveis de coordenação. A capacidade de disponibilizar a informação e a frequência de contato entre os profissionais são elementos importantes para o cuidado abrangente, contínuo e de qualidade.

[The Madrid autonomous community epidemiological bulletin. A survey on its dissemination and opinion thereof on among primary care physicians for the year 2000].

PubMed

Fernández Rodríguez, Silvia; Zorrilla Torras, Belén; Ramírez Fernández, Rosa; Alvarez Castillo, M Carmen; López-Gay Lucio, Dulce; Ibáñez Martín, Cosuelo; Bueno Vallejos, Rafael

2002-01-01

The Autonomous Community of Madrid Epidemiological Bulletin is the main communications link between epidemiological monitoring system and health care professionals. The purpose of this study is that of ascertaining the dissemination and opinion of this Autonomous Community of Madrid Epidemiological Bulletin among primary care physicians for the purpose of adapting this publication to its readers' interests. A telephone survey among primary care physicians in the Autonomous Community of Madrid, asking how often they read the Bulletin, the interest and usefulness of the information included in it. The sample size was estimated at 346 physicians. A two-stage sampling process was carried out-by cluster sampling in the first stage, randomly selecting 125 health care centers and 2.7 physicians per center, 17% being primary care team coordinators. A comparison is made of the results among physicians and coordinators by means of the Chi-square and Fisher's Exact Test method, with Epi-Info v.6. A total of 305 surveys were conducted (245 physicians and 60 coordinators). There was an awareness of the existence of the Autonomous Community of Madrid Epidemiological Bulletin on the part of 91.5% (CI 95%: 88.1-94.8), and 27.2% (CI 95%: 21.9-32.5) were familiar with more than 50% of the last issues published. A total of 92.4% (CI 95%: 89.4-95.8) considered the Bulletin to be interesting or highly interesting, grading its usefulness an average of 3.5 on a maximum scale of 5. Of the permanent sections, the most highly-valued was Epidemic Outbreaks, those reports related to meningococcal infection, tuberculosis and HIV/AIDS being the most highly-valued. The Autonomous Community of Madrid Epidemiological Bulletin is a publication which, although not widely-known by the primary care physicians in the Community, is well-valued when it is read, thus being a useful feedback tool within the Epidemiological Monitoring System.

Nanoscale Assembly of Actuating Cilia-Mimetic

NASA Astrophysics Data System (ADS)

Baird, Lance; Breidenich, Jennifer; Land, Bruce; Hayes, Allen; Benkoski, Jason; Keng, Pei; Pyun, Jeffrey

2009-03-01

The cilium is among the smallest mechanical actuators found in nature. We have taken inspiration from this design to create magnetic nanochains, measuring approximately 1-5 μm long and 25 nm in diameter. Fabricated from the self-assembly of cobalt nanoparticles, these flexible filaments actuate in an oscillating magnetic field. The cobalt nanoparticles were functionalized with a polystyrene/benzaldehyde surface coating, thus allowing the particles to form imine bonds with one another in the presence of a diamine terminated polyethylene glycol. These imine bonds effectively cross-linked the particles and held the nanochains together in the absence of a magnetic field. Using design of experiments (DOE) to efficiently screen the effects of cobalt nanoparticle concentration, crosslinker concentration, and surface chemistry, we determined that the morphology of the final structures could be explained primarily by physical interactions (i.e. magnetic forces) rather than chemistry.

Medicaid Managed Care Structures and Care Coordination.

PubMed

Gilchrist-Scott, Douglas H; Feinstein, James A; Agrawal, Rishi

2017-09-01

Child enrollment in Medicaid managed care (MMC) has expanded dramatically, primarily through state mandates. Care coordination is a key metric in MMC evaluation because it drives much of the proposed cost savings and may be associated with improved health outcomes and utilization. We evaluated the relationships between enrollment in 2 MMC structures, primary care case management (PCCM) and health maintenance organization (HMO) and access to and receipt of care coordination by children. Using data from the 2011/2012 National Survey of Children's Health and the Medicaid Statistical Information System state data mart, we conducted a retrospective, cross-sectional analysis of the relationships between fee-for-service, PCCM or HMO enrollment, and access to and receipt of care coordination. State-level univariate analyses and individual and state multilevel multivariable analyses evaluated correlations between MMC enrollment and care coordination, controlling for demographic characteristics and state financing levels. In univariate and multilevel multivariable analyses, the PCCM penetration rate was significantly associated with increased access to care coordination (adjusted odds ratio: 1.23, P = .034) and receipt of care coordination (adjusted odds ratio: 1.37, P = .02). The HMO penetration rate was significantly associated with lower access to care coordination (adjusted odds ratio: 0.85, P = .05) and receipt of care coordination (adjusted odds ratio: 0.71, P < .001). Fee-for-service served as the referent. State utilization of MMC varied widely. These data suggest that care coordination may be more effective in PCCM than HMO structures. States should consider care coordination outcomes when structuring their Medicaid programs. Copyright © 2017 by the American Academy of Pediatrics.

Investigation of Primary School Teachers' Attitudes towards Gifted Education=Ilkögretim Ögretmenlerinin Üstün Yeteneklilerin Egitimine Iliskin Tutumlarinin Incelenmesi

ERIC Educational Resources Information Center

Tortop, Hasan Said; Kunt, Kürsat

2013-01-01

Gifted education is very important issue for the development of societies. This importance has been increased with opening of the Center for Science and Art in Turkey. These institutions provide with formal educational institutions coordination for development of gifted students. In this respect, primary school teachers' attitude towards gifted…

Ecological and Intercultural Citizenship in the Primary English as a Foreign Language (EFL) Classroom: An Online Project in Argentina

ERIC Educational Resources Information Center

Porto, Melina

2016-01-01

This article describes an online intercultural citizenship project concerning the environment in the primary English-language classroom carried out in 2013/2014 between Argentina and Denmark. It is part of a network of projects coordinated by Michael Byram that involves teachers and researchers in Europe, the US and East Asia. The project is…

Older Patients' Perspectives on Quality of Serious Illness Care in Primary Care.

PubMed

Abu Al Hamayel, Nebras; Isenberg, Sarina R; Hannum, Susan M; Sixon, Joshua; Smith, Katherine Clegg; Dy, Sydney M

2018-01-01

Despite increased focus on measuring and improving quality of serious illness care, there has been little emphasis on the primary care context or incorporation of the patient perspective. To explore older patients' perspectives on the quality of serious illness care in primary care. Qualitative interview study. Twenty patients aged 60 or older who were at risk for or living with serious illness and who had participated in the clinic's quality improvement initiative. We used a semistructured, open-ended guide focusing on how older patients perceived quality of serious illness care, particularly in primary care. We transcribed interviews verbatim and inductively identified codes. We identified emergent themes using a thematic and constant comparative method. We identified 5 key themes: (1) the importance of patient-centered communication, (2) coordination of care, (3) the shared decision-making process, (4) clinician competence, and (5) access to care. Communication was an overarching theme that facilitated coordination of care between patients and their clinicians, empowered patients for shared decision-making, related to clinicians' perceived competence, and enabled access to primary and specialty care. Although access to care is not traditionally considered an aspect of quality, patients considered this integral to the quality of care they received. Patients perceived serious illness care as a key aspect of quality in primary care. Efforts to improve quality measurement and implementation of quality improvement initiatives in serious illness care should consider these aspects of care that patients deem important, particularly communication as an overarching priority.

Experiences with primary healthcare in Fuzhou, urban China, in the context of health sector reform: a mixed methods study.

PubMed

McCollum, Rosalind; Chen, Lieping; ChenXiang, Tang; Liu, Xiaoyun; Starfield, Barbara; Jinhuan, Zheng; Tolhurst, Rachel

2014-01-01

China has recently placed increased emphasis on the provision of primary healthcare services through health sector reform, in response to inequitably distributed health services. With increasing funding for community level facilities, now is an opportune time to assess the quality of primary care delivery and identify areas in need of further improvement. A mixed methodology approach was adopted for this study. Quantitative data were collected using the Primary Care Assessment Tool-Chinese version (C-PCAT), a questionnaire previously adapted for use in China to assess the quality of care at each health facility, based on clients' experiences. In addition, qualitative data were gathered through eight semi-structured interviews exploring perceptions of primary care with health directors and a policy maker to place this issue in the context of health sector reform. The study found that patients attending community health and sub-community health centres are more likely to report better experiences with primary care attributes than patients attending hospital facilities. Generally low scores for community orientation, family centredness and coordination in all types of health facility indicate an urgent need for improvement in these areas. Healthcare directors and policy makers perceived the need for greater coordination between levels of health providers, better financial reimbursement, more formal government contracts and recognition/higher status for staff at the community level and more appropriate undergraduate and postgraduate training. Copyright © 2013 John Wiley & Sons, Ltd.

Improving Care Teams' Functioning: Recommendations from Team Science.

PubMed

Fiscella, Kevin; Mauksch, Larry; Bodenheimer, Thomas; Salas, Eduardo

2017-07-01

Team science has been applied to many sectors including health care. Yet there has been relatively little attention paid to the application of team science to developing and sustaining primary care teams. Application of team science to primary care requires adaptation of core team elements to different types of primary care teams. Six elements of teams are particularly relevant to primary care: practice conditions that support or hinder effective teamwork; team cognition, including shared understanding of team goals, roles, and how members will work together as a team; leadership and coaching, including mutual feedback among members that promotes teamwork and moves the team closer to achieving its goals; cooperation supported by an emotionally safe climate that supports expression and resolution of conflict and builds team trust and cohesion; coordination, including adoption of processes that optimize efficient performance of interdependent activities among team members; and communication, particularly regular, recursive team cycles involving planning, action, and debriefing. These six core elements are adapted to three prototypical primary care teams: teamlets, health coaching, and complex care coordination. Implementation of effective team-based models in primary care requires adaptation of core team science elements coupled with relevant, practical training and organizational support, including adequate time to train, plan, and debrief. Training should be based on assessment of needs and tasks and the use of simulations and feedback, and it should extend to live action. Teamlets represent a potential launch point for team development and diffusion of teamwork principles within primary care practices. Copyright © 2017 The Joint Commission. Published by Elsevier Inc. All rights reserved.

[Strengthening primary health care: a strategy to maximize coordination of care].

PubMed

de Almeida, Patty Fidelis; Fausto, Márcia Cristina Rodrigues; Giovanella, Lígia

2011-02-01

To describe and analyze the actions developed in four large cities to strengthen the family health strategy (FHS) in Brazil. Case studies were carried out in Aracaju, Belo Horizonte, Florianópolis, and Vitória based on semi-structured interviews with health care managers. In addition, a cross-sectional study was conducted with questionnaires administered to a sample of FHS workers and services users. Actions needed to strengthen primary health care services were identified in all four cities. These include increasing the number of services offered at the primary health care level, removing barriers to access, restructuring primary services as the entry point to the health care system, enhancing problem-solving capacity (diagnostic and therapeutic support and networking between health units to organize the work process, training, and supervision), as well as improving articulation between surveillance and care actions. The cities studied have gained solid experience in the reorganization of the health care model based on a strengthening of health primary care and of the capacity to undertake the role of health care coordinator. However, to make the primary care level the customary entry point and first choice for users, additional actions are required to balance supplier-induced and consumer-driven demands. Consumer driven demand is the biggest challenge for the organization of teamwork processes. Support for and recognition of FHS as a basis for primary health care is still an issue. Initiatives to make FHS better known to the population, health care professionals at all levels, and civil society organizations are still needed.

75 FR 8176 - Shipping Coordinating Committee; Notice of Committee Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-23

..., SW., Washington, DC 20593-0001. The primary purpose of the meeting is to prepare for the sixtieth... matters to be considered include: --Harmful aquatic organisms in ballast water --Recycling of ships...

The oral healthcare manager in a patient-centered health facility

PubMed Central

Theile, Cheryl Westphal; Strauss, Shiela; Northridge, Mary Evelyn; Birenz, Shirley

2016-01-01

Background and Purpose Although dental hygienists are currently practicing within interprofessional teams in settings such as pediatric offices, hospitals, nursing homes, schools, and federally qualified health centers, they often still assume traditional responsibilities rather than practicing to the full extent of their training and licenses. This article explains the opportunity for the dental hygiene professional to embrace patient-centered care as an oral healthcare manager who can facilitate integration of oral and primary care in a variety of healthcare settings. Methods Based on an innovative model of collaboration between a college of dentistry and a college of nursing, an idea emerged among several faculty members for a new management method for realizing continuity and coordination of comprehensive patient care. Involved faculty members began working on the development of an approach to interprofessional practice with the dental hygienist serving as an oral healthcare manager who would address both oral healthcare and a patient’s related primary care issues through appropriate referrals and follow-up. This approach is explained in this article, along with the results of several pilot studies that begin to evaluate the feasibility of a dental hygienist as an oral healthcare manager. Conclusion A healthcare provider with management skills and leadership qualities is required to coordinate the interprofessional provision of comprehensive healthcare. The dental hygienist has the opportunity to lead closer integration of oral and primary care as an oral healthcare manager, by coordinating the team of providers needed to implement comprehensive, patient-centered care. PMID:27236994

Medical Home Transformation in Pediatric Primary Care—What Drives Change?

PubMed Central

McAllister, Jeanne W.; Cooley, W. Carl; Van Cleave, Jeanne; Boudreau, Alexy Arauz; Kuhlthau, Karen

2013-01-01

PURPOSE The aim of this study was to characterize essential factors to the medical home transformation of high-performing pediatric primary care practices 6 to 7 years after their participation in a national medical home learning collaborative. METHODS We evaluated the 12 primary care practice teams having the highest Medical Home Index (MHI) scores after participation in a national medical home learning collaborative with current MHI scores, a clinician staff questionnaire (assessing adaptive reserve), and semistructured interviews. We reviewed factors that emerged from interviews and analyzed domains and subdomains for their agreement with MHI and adaptive reserve domains and subthemes using a process of triangulation. RESULTS At 6 to 7 years after learning collaborative participation, 4 essential medical home attributes emerged as drivers of transformation: (1) a culture of quality improvement, (2) family-centered care with parents as improvement partners, (3) team-based care, and (4) care coordination. These high-performing practices developed comprehensive, family-centered, planned care processes including flexible access options, population approaches, and shared care plans. Eleven practices evolved to employ care coordinators. Family satisfaction appeared to stem from better access, care, and safety, and having a strong relationship with their health care team. Physician and staff satisfaction was high even while leadership activities strained personal time. CONCLUSIONS Participation in a medical home learning collaborative stimulated, but did not complete, medical home changes in 12 pediatric practices. Medical home transformation required continuous development, ongoing quality improvement, family partnership skills, an attitude of teamwork, and strong care coordination functions. PMID:23690392

[Evolution of burnout and associated factors in primary care physicians].

PubMed

Matía Cubillo, Angel Carlos; Cordero Guevara, José; Mediavilla Bravo, José Javier; Pereda Riguera, Maria José; González Castro, Maria Luisa; González Sanz, Ana

2012-09-01

To analyse the course of burnout and develop an explanatory model. Prospective cohort dynamics. SITE: All primary health care centres in Burgos. All physicians except medical emergencies, paediatrics and residents. Anonymous self-report questionnaire: Maslach Burnout Inventory (MBI) and related variables. An analysis was performed using the Student-t, X(2) test and logistic regression. The response rate was 47.76% in 2007, which was lower than that of 2005. There were significant differences between 2005 and 2007, for increases in the percentage of physicians who smoked, postgraduate training, residency, and those who believe that coordination with nursing and specialist care and institutional communication is appropriate. There was an increase in the prevalence of burnout by almost one point compared with 2005, a decrease in maximum burnout and emotional exhaustion (EC), and an increase in depersonalisation (DP) and personal accomplishment (RP). The incidence density of burnout was 1/113. 5 primary care physicians per year. The existence of burnout is associated with the use of chronic medication and inadequate coordination between nursing and EC, and also with the high workload. The increase in the prevalence found is consistent with the idea of burnout as a dynamic development and the theoretical model described. Stable and quality employment is one way to indirectly mitigate (by encouraging internal communication) professional burnout. In the multivariate analysis, the most critical variable in the onset of burnout is the inadequate coordination with nursing. Copyright © 2008 Elsevier España, S.L. All rights reserved.

The real-world problem of care coordination: a longitudinal qualitative study with patients living with advanced progressive illness and their unpaid caregivers.

PubMed

Daveson, Barbara A; Harding, Richard; Shipman, Cathy; Mason, Bruce L; Epiphaniou, Eleni; Higginson, Irene J; Ellis-Smith, Clare; Henson, Lesley; Munday, Dan; Nanton, Veronica; Dale, Jeremy R; Boyd, Kirsty; Worth, Allison; Barclay, Stephen; Donaldson, Anne; Murray, Scott

2014-01-01

To develop a model of care coordination for patients living with advanced progressive illness and their unpaid caregivers, and to understand their perspective regarding care coordination. A prospective longitudinal, multi-perspective qualitative study involving a case-study approach. Serial in-depth interviews were conducted, transcribed verbatim and then analyzed through open and axial coding in order to construct categories for three cases (sites). This was followed by continued thematic analysis to identify underlying conceptual coherence across all cases in order to produce one coherent care coordination model. Fifty-six purposively sampled patients and 27 case-linked unpaid caregivers. Three cases from contrasting primary, secondary and tertiary settings within Britain. Coordination is a deliberate cross-cutting action that involves high-quality, caring and well-informed staff, patients and unpaid caregivers who must work in partnership together across health and social care settings. For coordination to occur, it must be adequately resourced with efficient systems and services that communicate. Patients and unpaid caregivers contribute substantially to the coordination of their care, which is sometimes volunteered at a personal cost to them. Coordination is facilitated through flexible and patient-centered care, characterized by accurate and timely information communicated in a way that considers patients' and caregivers' needs, preferences, circumstances and abilities. Within the midst of advanced progressive illness, coordination is a shared and complex intervention involving relational, structural and information components. Our study is one of the first to extensively examine patients' and caregivers' views about coordination, thus aiding conceptual fidelity. These findings can be used to help avoid oversimplifying a real-world problem, such as care coordination. Avoiding oversimplification can help with the development, evaluation and implementation of real-world coordination interventions for patients and their unpaid caregivers in the future.

Care Coordination and Electronic Health Records: Connecting Clinicians

PubMed Central

Graetz, Ilana; Reed, Mary; Rundall, Thomas; Bellows, Jim; Brand, Richard; Hsu, John

2009-01-01

Objective: To examine the association between use of electronic health records (EHR) and care coordination. Study Design: Two surveys, in 2005 and again in 2006, of primary care clinicians working in a prepaid integrated delivery system during the staggered implementation of an EHR system. Using multivariate logistic regression to adjust for clinician characteristics, we examined the association between EHR use and clinicians’ perceptions of three dimensions of care coordination: timely access to complete information; treatment goal agreement; and role/responsibility agreement. Results: Compared to clinicians without EHR, clinicians with 6+ months of EHR use more frequently reported timely access to complete information, and being in agreement on treatment goals with other involved clinicians. There was no significant association between EHR use and being in agreement on roles and responsibilities with other clinicians. Conclusions: EHR use is associated with aspects of care coordination involving information transfer and communication of treatment goals. PMID:20351851

A regional programme to improve skin cancer management.

PubMed

McGeoch, Graham R; Sycamore, Mark J; Shand, Brett I; Simcock, Jeremy W

2015-12-01

In 2008, public specialist and general practice services in Canterbury were unable to manage demand for skin cancer treatment. Local clinicians decided the solution was to develop a see-and-treat skin excision clinic staffed by plastic surgeons and general practitioners (GPs), and the introduction of subsidised excisions in general practice. This paper describes the collaboration between clinicians, managers and funders and the results and quality management measures of these initiatives. There is an increasing incidence of skin cancer. GPs in Canterbury were unable to meet increasing demand for skin cancer treatment because some lacked confidence and competence in skin cancer management. There was no public funding for primary care management of skin cancer, driving patients to fully funded secondary care services. Secondary care services were at capacity, with no coordinated programme across primary and secondary care. The programme has resulted in a greater number of skin cancers being treated by the public health system, a reduction in waiting times for treatment, and fewer minor skin lesions being referred to secondary care. Quality measures have been achieved and are improving steadily. Development of the programme has improved working relationships between primary and secondary care clinicians. The strategy was to facilitate the working relationship between primary and secondary care and increase the capacity for skin lesion excisions in both sectors. Skin cancer management can be improved by a coordinated approach between primary and secondary care.

Hypomorphic Recessive Variants in SUFU Impair the Sonic Hedgehog Pathway and Cause Joubert Syndrome with Cranio-facial and Skeletal Defects.

PubMed

De Mori, Roberta; Romani, Marta; D'Arrigo, Stefano; Zaki, Maha S; Lorefice, Elisa; Tardivo, Silvia; Biagini, Tommaso; Stanley, Valentina; Musaev, Damir; Fluss, Joel; Micalizzi, Alessia; Nuovo, Sara; Illi, Barbara; Chiapparini, Luisa; Di Marcotullio, Lucia; Issa, Mahmoud Y; Anello, Danila; Casella, Antonella; Ginevrino, Monia; Leggins, Autumn Sa'na; Roosing, Susanne; Alfonsi, Romina; Rosati, Jessica; Schot, Rachel; Mancini, Grazia Maria Simonetta; Bertini, Enrico; Dobyns, William B; Mazza, Tommaso; Gleeson, Joseph G; Valente, Enza Maria

2017-10-05

The Sonic Hedgehog (SHH) pathway is a key signaling pathway orchestrating embryonic development, mainly of the CNS and limbs. In vertebrates, SHH signaling is mediated by the primary cilium, and genetic defects affecting either SHH pathway members or ciliary proteins cause a spectrum of developmental disorders. SUFU is the main negative regulator of the SHH pathway and is essential during development. Indeed, Sufu knock-out is lethal in mice, and recessive pathogenic variants of this gene have never been reported in humans. Through whole-exome sequencing in subjects with Joubert syndrome, we identified four children from two unrelated families carrying homozygous missense variants in SUFU. The children presented congenital ataxia and cerebellar vermis hypoplasia with elongated superior cerebellar peduncles (mild "molar tooth sign"), typical cranio-facial dysmorphisms (hypertelorism, depressed nasal bridge, frontal bossing), and postaxial polydactyly. Two siblings also showed polymicrogyria. Molecular dynamics simulation predicted random movements of the mutated residues, with loss of the native enveloping movement of the binding site around its ligand GLI3. Functional studies on cellular models and fibroblasts showed that both variants significantly reduced SUFU stability and its capacity to bind GLI3 and promote its cleavage into the repressor form GLI3R. In turn, this impaired SUFU-mediated repression of the SHH pathway, as shown by altered expression levels of several target genes. We demonstrate that germline hypomorphic variants of SUFU cause deregulation of SHH signaling, resulting in recessive developmental defects of the CNS and limbs which share features with both SHH-related disorders and ciliopathies. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Genetic Analysis Reveals a Hierarchy of Interactions between Polycystin-Encoding Genes and Genes Controlling Cilia Function during Left-Right Determination

PubMed Central

Grimes, Daniel T.; Keynton, Jennifer L.; Buenavista, Maria T.; Jin, Xingjian; Patel, Saloni H.; Kyosuke, Shinohara; Williams, Debbie J.; Hamada, Hiroshi; Hussain, Rohanah; Nauli, Surya M.; Norris, Dominic P.

2016-01-01

During mammalian development, left-right (L-R) asymmetry is established by a cilia-driven leftward fluid flow within a midline embryonic cavity called the node. This ‘nodal flow’ is detected by peripherally-located crown cells that each assemble a primary cilium which contain the putative Ca2+ channel PKD2. The interaction of flow and crown cell cilia promotes left side-specific expression of Nodal in the lateral plate mesoderm (LPM). Whilst the PKD2-interacting protein PKD1L1 has also been implicated in L-R patterning, the underlying mechanism by which flow is detected and the genetic relationship between Polycystin function and asymmetric gene expression remains unknown. Here, we characterize a Pkd1l1 mutant line in which Nodal is activated bilaterally, suggesting that PKD1L1 is not required for LPM Nodal pathway activation per se, but rather to restrict Nodal to the left side downstream of nodal flow. Epistasis analysis shows that Pkd1l1 acts as an upstream genetic repressor of Pkd2. This study therefore provides a genetic pathway for the early stages of L-R determination. Moreover, using a system in which cultured cells are supplied artificial flow, we demonstrate that PKD1L1 is sufficient to mediate a Ca2+ signaling response after flow stimulation. Finally, we show that an extracellular PKD domain within PKD1L1 is crucial for PKD1L1 function; as such, destabilizing the domain causes L-R defects in the mouse. Our demonstration that PKD1L1 protein can mediate a response to flow coheres with a mechanosensation model of flow sensation in which the force of fluid flow drives asymmetric gene expression in the embryo. PMID:27272319

Utilizing a Modified Care Coordination Measurement Tool to Capture Value for a Pediatric Outpatient Parenteral and Prolonged Oral Antibiotic Therapy Program.

PubMed

Vaz, Louise E; Farnstrom, Cindi L; Felder, Kimberly K; Guzman-Cottrill, Judith; Rosenberg, Hannah; Antonelli, Richard C

2017-04-17

Outpatient parenteral or prolonged oral antibiotic therapy (OPAT) programs reduce inpatient healthcare costs by shifting care to outpatient settings. Care coordination (CC) is a necessary component to successfully transition patients. Our objective was to assess outcomes of provider time spent on nonreimbursable CC activities in a pediatric OPAT program. We used a qualitative feasibility pilot design and modified the Care Coordination Measurement Tool. We captured nonreimbursable CC activity and associated outcome(s) among pediatric patients enrolled in OPAT from March 1 to April 30, 2015 (44 work days) at Doernbecher Children's Hospital. We generated summary statistics for this institutional review board-waived QI project. There were 154 nonreimbursable CC encounters conducted by 2 infectious diseases (ID) providers for 29 patients, ages 17 months-15 years, with complex infections. Total estimated time spent on CC was 54 hours, equivalent to at least 6 workdays. Five patients with complex social issues used 37% of total CC time. Of 129 phone events, 38% involved direct contact with families, pharmacies (13%), primary care providers (13%), and home health nursing (11%). Care coordination prevented 10 emergency room (ER) visits and 2 readmissions. Care coordination led to 16 additional, not previously scheduled subspecialist and 13 primary care visits. The OPAT providers billed for 32 clinic visits during the study period. Nonreimbursable CC work by OPAT providers prevented readmissions and ER visits and helped facilitate appropriate healthcare use. The value of pediatric OPAT involvement in patient care would have been underestimated based on reimbursable ID consultations and clinic visits alone. © The Author 2017. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Behavioral Health and the Comprehensive Primary Care (CPC) Initiative: findings from the 2014 CPC behavioral health survey.

PubMed

Zivin, Kara; Miller, Benjamin F; Finke, Bruce; Bitton, Asaf; Payne, Perry; Stowe, Edith C; Reddy, Ashok; Day, Timothy J; Lapin, Pauline; Jin, Janel L; Sessums, Laura L

2017-08-29

Incorporating behavioral health care into patient centered medical homes is critical for improving patient health and care quality while reducing costs. Despite documented effectiveness of behavioral health integration (BHI) in primary care settings, implementation is limited outside of large health systems. We conducted a survey of BHI in primary care practices participating in the Comprehensive Primary Care (CPC) initiative, a four-year multi-payer initiative of the Centers for Medicare and Medicaid Services (CMS). We sought to explore associations between practice characteristics and the extent of BHI to illuminate possible factors influencing successful implementation. We fielded a survey that addressed six substantive domains (integrated space, training, access, communication and coordination, treatment planning, and available resources) and five behavioral health conditions (depression, anxiety, pain, alcohol use disorder, and cognitive function). Descriptive statistics compared BHI survey respondents to all CPC practices, documented the availability of behavioral health providers, and primary care and behavioral health provider communication. Bivariate relationships compared provider and practice characteristics and domain scores. One hundred sixty-one of 188 eligible primary care practices completed the survey (86% response rate). Scores indicated basic to good baseline implementation of BHI in all domains, with lowest scores on communication and coordination and highest scores for depression. Higher scores were associated with: having any behavioral health provider, multispecialty practice, patient-centered medical home designation, and having any communication between behavioral health and primary care providers. This study provides useful data on opportunities and challenges of scaling BHI integration linked to primary care transformation. Payment reform models such as CPC can assist in BHI promotion and development.

Primary care models for treating opioid use disorders: What actually works? A systematic review

PubMed Central

Klasa, Katarzyna; Bush, Christopher; Heisler, Michele; Chopra, Vineet; Bohnert, Amy

2017-01-01

Background Primary care-based models for Medication-Assisted Treatment (MAT) have been shown to reduce mortality for Opioid Use Disorder (OUD) and have equivalent efficacy to MAT in specialty substance treatment facilities. Objective The objective of this study is to systematically analyze current evidence-based, primary care OUD MAT interventions and identify program structures and processes associated with improved patient outcomes in order to guide future policy and implementation in primary care settings. Data sources PubMed, EMBASE, CINAHL, and PsychInfo. Methods We included randomized controlled or quasi experimental trials and observational studies evaluating OUD treatment in primary care settings treating adult patient populations and assessed structural domains using an established systems engineering framework. Results We included 35 interventions (10 RCTs and 25 quasi-experimental interventions) that all tested MAT, buprenorphine or methadone, in primary care settings across 8 countries. Most included interventions used joint multi-disciplinary (specialty addiction services combined with primary care) and coordinated care by physician and non-physician provider delivery models to provide MAT. Despite large variability in reported patient outcomes, processes, and tasks/tools used, similar key design factors arose among successful programs including integrated clinical teams with support staff who were often advanced practice clinicians (nurses and pharmacists) as clinical care managers, incorporating patient “agreements,” and using home inductions to make treatment more convenient for patients and providers. Conclusions The findings suggest that multidisciplinary and coordinated care delivery models are an effective strategy to implement OUD treatment and increase MAT access in primary care, but research directly comparing specific structures and processes of care models is still needed. PMID:29040331

Minding the gap and overlap: a literature review of fragmentation of primary care for chronic dialysis patients.

PubMed

Wang, Virginia; Diamantidis, Clarissa J; Wylie, JaNell; Greer, Raquel C

2017-08-29

Care coordination is a challenge for patients with kidney disease, who often see multiple providers to manage their associated complex chronic conditions. Much of the focus has been on primary care physician (PCP) and nephrologist collaboration in the early stages of chronic kidney disease, but less is known about the co-management of the patients in the end-stage of renal disease. We conducted a systematic review and synthesis of empirical studies on primary care services for dialysis patients. Systematic literature search of MEDLINE/PubMED, CINAHL, and EmBase databases for studies, published until August 2015. Inclusion criteria included publications in English, empirical studies involving human subjects (e.g., patients, physicians), conducted in US and Canadian study settings that evaluated primary care services in the dialysis patient population. Fourteen articles examined three major themes of primary care services for dialysis patients: perceived roles of providers, estimated time in providing primary care, and the extent of dialysis patients' use of primary care services. There was general agreement among providers that PCPs should be involved but time, appropriate roles, and miscommunication are potential barriers to good primary care for dialysis patients. Although many dialysis patients report having a PCP, the majority rely on primary care from their nephrologists. Studies using administrative data found lower rates of preventive care services than found in studies relying on provider or patient self-report. The extant literature revealed gaps and opportunities to optimize primary care services for dialysis patients, foreshadowing the challenges and promise of Accountable Care / End-Stage Seamless Care Organizations and care coordination programs currently underway in the United States to improve clinical and logistical complexities of care for this commonly overlooked population. Studies linking the relationship between providers and patients' receipt of primary care to outcomes will serve as important comparisons to the nascent care models for ESRD patients, whose value is yet to be determined.

"Attention on the flight deck": what ambulatory care providers can learn from pilots about complex coordinated actions.

PubMed

Frankel, Richard M; Saleem, Jason J

2013-12-01

Technical and interpersonal challenges of using electronic health records (EHRs) in ambulatory care persist. We use cockpit communication as an example of highly coordinated complex activity during flight and compare it with providers' communication when computers are used in the exam room. Maximum variation sampling was used to identify two videotapes from a parent study of primary care physicians' exam room computer demonstrating the greatest variation. We then produced and analyzed visualizations of the time providers spent looking at the computer and looking at the patient. Unlike the cockpit which is engineered to optimize joint attention on complex coordinated activities, we found polar extremes in the use of joint focus of attention to manage the medical encounter. We conclude that there is a great deal of room for improving the balance of interpersonal and technical attention that occurs in routine ambulatory visits in which computers are present in the exam room. Using well-known aviation practices can help primary care providers become more aware of the opportunities and challenges for enhancing the physician patient relationship in an era of exam room computing. Published by Elsevier Ireland Ltd.

Synthesis, Structure, and Physical Properties for a Series of Monomeric Iron(III) Hydroxo Complexes with Varying Hydrogen-Bond Networks

PubMed Central

Mukherjee, Jhumpa; Lucas, Robie L.; Zart, Matthew K.; Powell, Douglas R.; Day, Victor W.; Borovik, A. S.

2013-01-01

Mononuclear iron(III) complexes with terminal hydroxo ligands are proposed to be important species in several metalloproteins, but they have been difficult to isolate in synthetic systems. Using a series of amidate/ureido tripodal ligands, we have prepared and characterized monomeric FeIIIOH complexes with similar trigonal-bipyramidal primary coordination spheres. Three anionic nitrogen donors define the trigonal plane, and the hydroxo oxygen atom is trans to an apical amine nitrogen atom. The complexes have varied secondary coordination spheres that are defined by intramolecular hydrogen bonds between the FeIIIOH unit and the urea NH groups. Structural trends were observed between the number of hydrogen bonds and the Fe–Ohydroxo bond distances: the more intramolecular hydrogen bonds there were, the longer the Fe–O bond became. Spectroscopic trends were also found, including an increase in the energy of the O–H vibrations with a decrease in the number of hydrogen bonds. However, the FeIII/II reduction potentials were constant throughout the series (∼2.0 V vs [Cp2Fe]0/+1), which is ascribed to a balancing of the primary and secondary coordination-sphere effects. PMID:18498155

Effects of handedness (left vs right) and cannabis abuse on intermanual coordination and negative symptoms in schizophrenic patients of the paranoid type.

PubMed

Gorynia, Inge; Schwaiger, Markus

2011-09-01

Intermanual coordination as an index of interhemispheric transfer and negative symptoms were investigated in 50 left- and 42 right-handed schizophrenic inpatients of the paranoid type, also including drug abusers. The primary objective was to show that there were higher values in intermanual coordination and fewer manifestations of negative symptoms in the left-handed compared to the right-handed patients. This assumption was based on previous studies. Most importantly, right- and left-handed patients showed a different behaviour in intermanual coordination, when the duration of illness was taken into consideration. Thus, long-term left-handed paranoid patients performed better in intermanual coordination and showed fewer manifestations of negative symptoms than did long-term right-handed patients. These results were true for the large group of all patients, and among them for the subgroup of patients without drug abuse. Consequently, higher scores in intermanual coordination in left-handed patients may be related to a better interhemispheric crosstalk resulting in less pronounced negative symptoms. Secondary objectives assessed by explorative data analysis included the effects of cannabis abuse. While cannabis abuse may be more prevalent in left-handed patients, its effects may be more pronounced in right-handed patients, scoring higher in intermanual coordination and lower in manifestations of negative symptoms.

Counseling and Wellness Services Integrated with Primary Care: A Delivery System That Works

PubMed Central

Van Beek, Ken; Duchemin, Steve; Gersh, Geniene; Pettigrew, Susanne; Silva, Pamela; Luskin, Barb

2008-01-01

Introduction: The continuity and coordination of care between medical and behavioral health services is a major issue facing our health care delivery system. Barriers to basic communication between providers of medical services and providers of behavioral health services, include: no coordination of services, and poor recognition of the relationship between medical and behavioral issues. Methods: Colocating behavioral health counselors and nutritionists alongside primary care physicians and clinicians (PCPs). Results: Grand Valley Health Plan (GVHP) established the national benchmark for patients using ambulatory services for mental health, and ranked first in Michigan on all six HEDIS “effectiveness of care” measures for behavioral health. One result was a 54% decrease in mental health hospitalization. Discussion: Up to 70% of primary care visits are driven by psychosocial factors, with 25% of patients having a diagnosable mental disorder, and comorbidity occurring in up to 80%. With colocated services, PCPs now often explain to patients that “this is just how we deliver care to you,” when introducing health coaches to patients and asking them to be involved. PMID:21339917

Increasing the Capacity of Primary Care Through Enabling Technology.

PubMed

Young, Heather M; Nesbitt, Thomas S

2017-04-01

Primary care is the foundation of effective and high-quality health care. The role of primary care clinicians has expanded to encompass coordination of care across multiple providers and management of more patients with complex conditions. Enabling technology has the potential to expand the capacity for primary care clinicians to provide integrated, accessible care that channels expertise to the patient and brings specialty consultations into the primary care clinic. Furthermore, technology offers opportunities to engage patients in advancing their health through improved communication and enhanced self-management of chronic conditions. This paper describes enabling technologies in four domains (the body, the home, the community, and the primary care clinic) that can support the critical role primary care clinicians play in the health care system. It also identifies challenges to incorporating these technologies into primary care clinics, care processes, and workflow.

United States Department of State Strategic Plan

DTIC Science & Technology

1998-01-01

employment sources such as temporary hires, family member appointments, telecommuting , part- time and jobsharing arrangements, and contracts...primary responsibility for coordination and oversight with respect to science and technology agreements with foreign governments. GOAL: Stabilize

Intermedia: Tomorrow's AV Experience Today

ERIC Educational Resources Information Center

McVey, G. F.

1970-01-01

The coordinator of the Multimedia Instructional Laboratory at Wisconsin describes an experimental course whose primary objective was to expose through direct student participation the relationships and processes involved when messages are presented through several media simultaneously." (Author/LS)

77 FR 52105 - Shipping Coordinating Committee; Notice of Committee Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-28

... Building, 2100 Second Street SW., Washington, DC, 20593. The primary purpose of the meeting is to prepare... organisms in ballast water; --Recycling of ships; --Air pollution and energy efficiency; --Reduction of GHG...

77 FR 54648 - Shipping Coordinating Committee; Notice of Committee Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-05

... Building, 2100 Second Street SW., Washington, DC 20593. The primary purpose of the meeting is to prepare... organisms in ballast water; --Recycling of ships; --Air pollution and energy efficiency; --Reduction of GHG...

78 FR 14400 - Shipping Coordinating Committee; Notice of Committee Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-05

..., 2100 Second Street SW., Washington, DC, 20593. The primary purpose of the meeting is to prepare for the... ballast water; --Recycling of ships; --Air pollution and energy efficiency; --Reduction of GHG emissions...

Caring for Children with Medical Complexity: Perspectives of Primary Care Providers.

PubMed

Foster, Carolyn C; Mangione-Smith, Rita; Simon, Tamara D

2017-03-01

To describe typical care experiences and key barriers and facilitators to caring for children with medical complexity (CMC) from the perspective of community primary care providers (PCPs). PCPs participating in a randomized controlled trial of a care-coordination intervention for CMC were sent a 1-time cross-sectional survey that asked PCPs to (1) describe their experiences with caring for CMC; (2) identify key barriers affecting their ability to care for CMC; and (3) prioritize facilitators enhancing their ability to provide care coordination for CMC. PCP and practice demographics also were collected. One hundred thirteen of 155 PCPs sent the survey responded fully (completion rate = 73%). PCPs endorsed that medical characteristics such as polypharmacy (88%), multiorgan system involvement (84%), and rare/unfamiliar diagnoses (83%) negatively affected care. Caregivers with high needs (88%), limited time with patients and caregivers (81%), and having a large number of specialists involved in care (79%) were also frequently cited. Most commonly endorsed strategies to improve care coordination included more time with patients/caregivers (84%), summative action plans (83%), and facilitated communication (eg, e-mail, phone meetings) with specialists (83%). Community PCPs prioritized more time with patients and their families, better communication with specialists, and summative action plans to improve care coordination for this vulnerable population. Although this study evaluated perceptions rather than actual performance, it provides insights to improve understanding of which barriers and facilitators ideally might be targeted first for care delivery redesign. Copyright © 2016 Elsevier Inc. All rights reserved.

Delivering Coordinated Cancer Care by Building Transactive Memory in a Team of Teams.

PubMed

Henry, Elizabeth; Silva, Abigail; Tarlov, Elizabeth; Czerlanis, Cheryl; Bernard, Margie; Chauhan, Cynthia; Schalk, Denise; Stewart, Greg

2016-11-01

Cancer care delivery is highly complex. Treatment involves coordination within oncology health-care teams and across other teams of referring primary and specialty providers (a team of teams). Each team interfaces with patients and caregivers to offer component parts of comprehensive care. Because patients frequently obtain specialty care from divergent health-care systems resulting in cross-system health-care use, oncology teams need mechanisms to coordinate and collaborate within and across health-care systems to optimize clinical outcomes for all cancer patients. Transactive memory is one potential strategy that can help improve comprehensive patient care delivery. Transactive memory is a process by which two or more team professionals develop a shared system for encoding, storing, and retrieving information. Each professional is responsible for retaining only part of the total information. Applying this concept to a team of teams results in system benefits wherein all teams share an understanding of specialized knowledge held by each component team. The patient's role as the unifying member of the team of teams is central to successful treatment delivery. This clinical case presents a patient who is receiving oral treatment for advanced prostate cancer within two health systems. The case emphasizes the potential for error when multiple teams function without a point team (the team coordinating efforts of all other primary and specialty teams) and when the specialty knowledge of providers and patients is not well integrated into all phases of the care delivery process.

Motor coordination and balance in rodents.

PubMed

Carter, R J; Morton, J; Dunnett, S B

2001-08-01

Measurement of motor coordination and balance can be used not only to assess the effect of drugs or other experimental manipulations on mice and rats, but also to characterize the motor phenotype of transgenic or knock-out animals. Three well established and widely used protocols for measuring motor coordination and balance in mice and rats (rotarod, beam walking and footprint analysis) are described in this unit. The tests can be used equally well for rats and mice, and have been used both for the phenotypic characterization of transgenic mice and for evaluating the effects of lesions and aging in rats. The protocols are described in the primary context of testing mice, but modifications of the test apparatus or variations in the test parameters for assessment of rats are noted.

Hand preference consistency and simple rhythmic bimanual coordination in preschool children.

PubMed

Mori, Shiro; Iteya, Misaki; Gabbard, Carl

2007-06-01

This study examined whether strength of hand preference is associated with rhythmic bimanual coordination. 27 preschool children ages 4 to 6 years, identified as 10 right-, 8 left-, and 9 mixed-handed, were evaluated on accuracy and stability with a bimanual tapping task requiring intermodal matching. The primary hypothesis was that consistent right- and left-handers would have an advantage over mixed-handers given higher hemispheric maturation, possibly the corpus callosum, which may be the main interhemispheric communication conduit. A significant difference was noted among the three groups, with right-handers having higher accuracy and stability. This finding suggests that bimanual coordination in young children may be influenced by handedness, which may also be related to the development of interhemispheric communication.

A coordinated PCP-Cardiologist Telemedicine Model (PCTM) in China's community hypertension care: study protocol for a randomized controlled trial.

PubMed

Xu, Lei; Fang, Wei-Yi; Zhu, Fu; Zhang, Hong-Guang; Liu, Kai

2017-05-25

Hypertension is a major risk factor for cardiovascular disease, and its control rate has remained low worldwide. Studies have found that telemonitoring blood pressure (BP) helped control hypertension in randomized controlled trials. However, little is known about its effect in a structured primary care model in which primary care physicians (PCPs) are partnering with cardiology specialists in electronic healthcare data sharing and medical interventions. This study aims to identify the effects of a coordinated PCP-cardiologist model that applies telemedicine tools to facilitate community hypertension control in China. Patients with hypertension receiving care at four community healthcare centers that are academically affiliated to Shanghai Chest Hospital, Shanghai JiaoTong University are eligible if they have had uncontrolled BP in the previous 3 months and access to mobile Internet. Study subjects are randomly assigned to three interventional groups: (1) usual care; (2) home-based BP telemonitor with embedded Global System for Mobile Communications (GSM) module and unlimited data plan, an app to access personal healthcare record and receive personalized lifestyle coaching contents, and proficiency training of their use; or (3) this plus coordinated PCP-cardiologist care in which PCPs and cardiologists share data via a secure CareLinker website to determine interventional approaches. The primary outcome is mean change in systolic blood pressure over a 12-month period. Secondary outcomes are changes of diastolic blood pressure, HbA1C, blood lipids, and medication adherence measured by the eight-item Morisky Medication Adherence Scale. This study will determine whether a coordinated PCP-Cardiologist Telemedicine Model that incorporates the latest telemedicine technologies will improve hypertension care. Success of the model would help streamline the present community healthcare processes and impact a greater number of patients with uncontrolled hypertension. ClinicalTrials.gov, NCT02919033 . Registered on 23 September 2016.

Documenting coordination of cancer care between primary care providers and oncology specialists in Canada.

PubMed

Brouwers, Melissa C; Vukmirovic, Marija; Tomasone, Jennifer R; Grunfeld, Eva; Urquhart, Robin; O'Brien, Mary Ann; Walker, Melanie; Webster, Fiona; Fitch, Margaret

2016-10-01

To report on the findings of the CanIMPACT (Canadian Team to Improve Community-Based Cancer Care along the Continuum) Casebook project, which systematically documented Canadian initiatives (ie, programs and projects) designed to improve or support coordination and continuity of cancer care between primary care providers (PCPs) and oncology specialists. Pan-Canadian environmental scan. Canada. Individuals representing the various initiatives provided data for the analysis. Initiatives included in the Casebook met the following criteria: they supported coordination and collaboration between PCPs and oncology specialists; they were related to diagnosis, treatment, survivorship, or personalized medicine; and they included breast or colorectal cancer or both. Data were collected on forms that were compiled into summaries (ie, profiles) for each initiative. Casebook initiatives were organized based on the targeted stage of the cancer care continuum, jurisdiction, and strategy (ie, model of care or type of intervention) employed. Thematic analysis identified similarities and differences among employed strategies, the level of primary care engagement, implementation barriers and facilitators, and initiative evaluation. The CanIMPACT Casebook profiles 24 initiatives. Eleven initiatives targeted the survivorship stage of the cancer care continuum and 15 focused specifically on breast or colorectal cancer or both. Initiative teams implemented the following strategies: nurse patient navigation, multidisciplinary care teams, electronic communication or information systems, PCP education, and multicomponent initiatives. Initiatives engaged PCPs at various levels. Implementation barriers included lack of care standardization across jurisdictions and incompatibility among electronic communication systems. Implementation facilitators included having clinical and program leaders publicly support the initiative, repurposing existing resources, receiving financial support, and establishing a motivated and skilled project or program team. The lack of evaluative data made it difficult to identify the most effective interventions or models of care. The CanIMPACT Casebook documents Canadian efforts to improve or support the coordination of cancer care by PCPs and oncology specialists as a means to improve patient outcomes and cancer system performance. Copyright© the College of Family Physicians of Canada.