Upper Nasal Hemifield Location and Nonspatial Auditory Tones Accelerate Visual Detection during Dichoptic Viewing

Visual performance is asymmetric across the visual field, but locational biases that occur during dichoptic viewing are not well understood. In this study, we characterized horizontal, vertical and naso-temporal biases in visual target detection during dichoptic stimulation and explored whether the detection was facilitated by non-spatial auditory tones associated with the target's location. The detection time for single monocular targets that were suppressed from view with a 10 Hz dynamic noise mask presented to the other eye was measured at the 4 degrees intercardinal location of each eye with the breaking Continuous Flash Suppression (b-CFS) technique. Each target was either combined with a sound (i.e., high or low pitch tone) that was congruent or incongruent with its vertical location (i.e., upper or lower visual field) or presented without a sound. The results indicated faster detection of targets in the upper rather than lower visual field and faster detection of targets in the nasal than temporal hemifield of each eye. Sounds generally accelerated target detection, but the tone pitch-elevation congruency did not further enhance performance. These findings suggest that visual detection during dichoptic viewing differs from standard viewing conditions with respect to location-related perceptual biases and crossmodal modulation of visual perception. These differences should be carefully considered in experimental designs employing dichoptic stimulation techniques and in display applications that utilize dichoptic viewing.Peer reviewe

Differential Regulation of Decorin and Biglycan Gene Expression by Dexamethasone and Retinoic Acid in Cultured Human Skin Fibroblasts

Proteoglycans participate in the assembly of extracellular matrix, directly by interacting with other matrix components and indirectly by regulating cellular growth-factor responses. We have studied the regulation of gene expression of two small extracellular matrix chondroitin/dermatan sulfate proteoglycans, decorin and biglycan, by dexamethasone and retinoic acid In cultured human skin fibroblasts. Dexamethasone increased decorin production, maximally 4,8- fold, and decorin mRNA levels up to 2.3-fold, but had no effect on biglycan production or mRNA levels. Dexamethasone also prevented transforming growth factor-β-elicited down-regulation of decorin mRNA levels and production by dermal fibroblasts. In addition, dexamethasone potently inhibited enhancement of biglycan production and mRNA levels by transforming growth factor-β. Retinoic acid dose dependently reduced decorin mRNA levels (by 51%) and production (by 72%), but had no effect on biglycan gene expression. Retinoic acid did not alter the effect of transforming growth factor-β on decorin or biglycan production or mRNA levels. These results provide evidence that tile effects of glucocorticoids and retinoids on dermal connective tissue are partially mediated via altered expression of decorin and biglycan, which both in turn regulate the activity of transforming growth factor-β, the most potent stimulator of connective tissue deposition

Transforming Growth Factor-β Induces Collagenase-3 Expression by Human Gingival Fibroblasts via p38 Mitogen-activated Protein Kinase

Human collagenase-3 (matrix metalloproteinase 13 (MMP-13)) is characterized by exceptionally wide substrate specificity and restricted tissue specific expression. Human skin fibroblasts in culture express MMP-13 only when they are in three-dimensional collagen (Ravanti, L., Heino, J., Lopez-Otin, C., and Kahari. V.-M. (1999) J. Biol. Chem. 274, 2446-2455). Here we show that MMP-13 is expressed by fibroblasts during normal human gingival wound repair. Expression of MMP-13 by human gingival fibroblasts cultured in monolayer or in collagen gel was induced by transforming growth factor-beta1 (TGF-beta1). Treatment of gingival fibroblasts with TGF-beta1 activated two distinct mitogen-activated protein kinases (MAPKs): extracellular signal-regulated kinase 1/2 (ERK1/2) in 15 min and p38 MAPK in 1 and 2 h. Induction of MMP-13 expression by TGF-beta1 was blocked by SB203580, a specific inhibitor of p38 MAPK, but not by PD98059, a selective inhibitor of ERK1/2 activation. Adenovirus-mediated expression of dominant negative p38alpha and c-Jun potently inhibited induction of MMP-13 expression in gingival fibroblasts by TGF-beta1. Infection of gingival fibroblasts with adenovirus for constitutively active MEK1 resulted in activation of ERK1/2 and JNK1 and up-regulation of collagenase-1 (MMP-1) and stromelysin-1 (MMP-3) production but did not induce MMP-13 expression. In addition, activation of p38 MAPK by constitutively active MKK6b or MKK3b was not sufficient to induce MMP-13 expression. These results show that TGF-beta-elicited induction of MMP-13 expression by gingival fibroblasts is dependent on the activity of p38 MAPK and the presence of functional AP-1 dimers. These observations demonstrate a fundamental difference in the regulation of collagenolytic capacity between gingival and dermal fibroblasts and suggest a role for MMP-13 in rapid turnover of collagenous matrix during repair of gingival wounds, which heal with minimal scarring

Macromolecular crowding regulates matrix composition and gene expression in human gingival fibroblast cultures

Abstract Standard cell cultures are performed in aqueous media with a low macromolecule concentration compared to tissue microenvironment. In macromolecular crowding (MMC) experiments, synthetic polymeric crowders are added into cell culture media to better mimic macromolecule concentrations found in vivo. However, their effect on cultured cells is incompletely understood and appears context-dependent. Here we show using human gingival fibroblasts, a cell type associated with fast and scarless wound healing, that MMC (standard medium supplemented with Ficoll 70/400) potently modulates fibroblast phenotype and extracellular matrix (ECM) composition compared to standard culture media (nMMC) over time. MMC significantly reduced cell numbers, but increased accumulation of collagen I, cellular fibronectin, and tenascin C, while suppressing level of SPARC (Secreted Protein Acidic and Cysteine Rich). Out of the 75 wound healing and ECM related genes studied, MMC significantly modulated expression of 25 genes compared to nMMC condition. MMC also suppressed myofibroblast markers and promoted deposition of basement membrane molecules collagen IV, laminin 1, and expression of LAMB3 (Laminin Subunit Beta 3) gene. In cell-derived matrices produced by a novel decellularization protocol, the altered molecular composition of MMC matrices was replicated. Thus, MMC may improve cell culture models for research and provide novel approaches for regenerative therapy

Fysioterapeutin suoravastaanotto

Lähtökohdat - Fysioterapeutin suoravastaanotolla tarkoitetaan tuki- ja liikuntaelin (TULE) -potilaan ohjaamista ensisijaisesti fysioterapeutille lääkärin sijaan. Tutkimuksessa selvitettiin, onko fysioterapeutin suoravastaanotto potentiaalinen palvelu pyrittäessä tehostamaan TULE-potilaiden hoitoa. Menetelmät - Keski-Suomen sairaanhoitopiirin alueella koulutettiin julkisen terveydenhuollon fysioterapeutteja suoravastaanottotyöhön vuosina 2012–13. Suoravastaanotto käynnistettiin koulutusprojektin jälkeen portaittain vuoden 2013 alusta. Tässä tutkimuksessa tarkasteltiin tietojärjestelmistä fysioterapeutin suoravastaanoton ja lääkärien TULE-potilaiden käyntitietoja vuonna 2014. Tulokset - Fysioterapeutin suoravastaanotto käsitti yhteensä 2 398 TULE-potilaskäyntiä vuoden aikana. Lääkärien avosairaanhoidon vastaanotoille tehtiin vastaavasti 302 873 käyntiä, joista TULE-potilaskäynneiksi oli kirjattu 50 822 (17 %). Fysioterapeutin suoravastaanoton osuus alueen TULE-potilaskäynneistä oli 5 %. Suoravastaanoton potilaista 4 % ohjattiin jatkohoitoon lääkärille. Päätelmät - Fysioterapeutin suoravastaanotolle on mahdollista päästä kaikissa TULE-sairauksissa Keski-Suomen sairaanhoitopiirin jokaisessa viidessä perusterveydenhuollon kuntayhtymässä. Toimintaa laajentamalla voidaan tehostaa TULE-potilaiden hoitoa ja vähentää lääkärien kuormitusta sekä mahdollisesti vähentää kustannuksia, sillä vain pienellä osalla suoravastaanotolle ohjautuneista potilaista todettiin tarve jatkohoitoon lääkärille.Background - Direct access to physiotherapy is a new healthcare service model where patients with musculoskeletal diseases are directed straight to a physiotherapist’s practice without seeing a physician first. The aim of this study was to evaluate if the direct access service has the potential to enhance musculoskeletal patients’ treatment. Methods - Between the years 2012–2013, 28 physiotherapists working in the public sector in Central Finland were trained to work in the direct access services. After the training, the direct access service model was launched during the year 2013. This study examines the data on patient visits to direct access and physician practices collected from the patient information system in 2014. Results - During the research period the number of direct access patient visits was 2398. At the same time, 50,822 visits of patients with musculoskeletal diseases to physicians’ practices were recorded, which is 17% of all visits (302,873). Thus, direct access visits accounted for 5% of musculoskeletal patient visits. Four percent of these were further referred to a physician. Conclusions - In Central Finland patients with musculoskeletal diseases have a possibility to access physical therapy without seeing a physician first. Direct access is still a small-scale service, because of a lack of resources. Expanding the service could speed up the treatment of musculoskeletal patients, decrease physician workloads and potentially lower healthcare costs, because only small proportions of direct access patients were found to be in need of physicians’ services.peerReviewe

Expression and Function of Connexin 43 in Human Gingival Wound Healing and Fibroblasts

<div><p>Connexins (C×s) are a family of transmembrane proteins that form hemichannels and gap junctions (GJs) on the cell membranes, and transfer small signaling molecules between the cytoplasm and extracellular space and between connecting cells, respectively. Among C×s, suppressing C×43 expression or function promotes skin wound closure and granulation tissue formation, and may alleviate scarring, but the mechanisms are not well understood. Oral mucosal gingiva is characterized by faster wound closure and scarless wound healing outcome as compared to skin wounds. Therefore, we hypothesized that C×43 function is down regulated during human gingival wound healing, which in fibroblasts promotes expression of genes conducive for fast and scarless wound healing. Cultured gingival fibroblasts expressed C×43 as their major connexin. Immunostaining of unwounded human gingiva showed that C×43 was abundantly present in the epithelium, and in connective tissue formed large C×43 plaques in fibroblasts. At the early stages of wound healing, C×43 was strongly down regulated in wound epithelial cells and fibroblasts, returning to the level of normal tissue by day 60 post-wounding. Blocking of C×43 function by C×43 mimetic peptide Gap27 suppressed GJ-mediated dye transfer, promoted migration, and caused significant changes in the expression of wound healing-associated genes in gingival fibroblasts. In particular, out of 54 genes analyzed, several MMPs and TGF-β1, involved in regulation of inflammation and extracellular matrix (ECM) turnover, and VEGF-A, involved in angiogenesis, were significantly upregulated while pro-fibrotic ECM molecules, including Collagen type I, and cell contractility-related molecules were significantly down regulated. These responses involved MAPK, GSK3α/β and TGF-β signaling pathways, and AP1 and SP1 transcription factors. Thus, suppressed function of C×43 in fibroblasts promotes their migration, and regulates expression of wound healing-associated genes via AP1, SP1, MAPK, GSK3α/β and TGF-β signaling pathways, and may promote fast and scarless wound healing in human gingiva.</p></div

Gap27 treatment increases C×43 protein abundance significantly.

<p>(A) Confluent cultures of gingival fibroblasts (GFBL-DC) were treated with Gap27 or control peptide (150 μM) for 24 h, and abundance of C×43 was analyzed by Western blotting. Gap27 treatment did not affect the relative intensities of three bands corresponding to differently phosphorylated forms of C×43 (P0: pS368; P1:pS279/282 and pS255; P2: pS262). (B) Quantitation of C×43 levels in Western blots shows mean +/− SEM from three independent experiments (**p<0.01; Student’s t-test). Sample loading was normalized for β-Tubulin levels.</p