Beyond Cartilage Repair: The Role of the Osteochondral Unit in Joint Health and Disease.

IMPACT STATEMENT: In this comprehensive review, we are providing a holistic overview of osteochondral tissue development, disease, pain localization, as well as structural evaluation and current repair strategies. This review is intended to serve as a broad introduction to this multidisciplinary research area. It is a thorough examination of the biological aspects of the osteochondral unit from a tissue engineering perspective, highlighting the importance of the subchondral bone in chondral and osteochondral lesion repair and pain relief.

[Adjuvant electrostimulation therapy for chronic rhinosinusitis]. / Adjuvante Elektrostimulationstherapie bei chronischer Rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis (CRS) is one of the most common chronic diseases in Germany and is often accompanied by years of chronic rhinosinusitis. According to the current German guideline "Rhinosinusitis", the nasal application of salt solutions, topical corticosteroids and in individual cases also systemic corticosteroids appear useful for a symptomatic therapy of CRS. The evidence for other therapeutic procedures such as acupuncture, homeopathy and phytotherapeutics is seen as insufficient. The aim of the present study was to investigate whether anti-inflammatory effects of electrostimulation therapy can also be demonstrated in CRS. METHODOLOGY: randomized, prospective single center study, primary setting; 16 patients with moderate chronic rhinosinusitis with polyps (cRScNP), corresponding to a Lund / Mackay score of 6-12; home based electrostimulation therapy (EST) with amplitude modulated current (base frequency of 4000 Hz, frequency band of 100-250 Hz) over 2 weeks adjuvant to a concurrent sinusitis therapy with topical corticosteroids; measurement of nasal nitric oxide concentration and self-assessment of complaints with the questionnaire instrument SNOT-20 GAV; survey points t0 before EST, t1 after EST, t2 6 weeks after t1. RESULTS: Home based EST was performed by 16 patients. The results indicate that the positive effects of electrostimulation therapy in inflammatory processes also exist in CRS. DISCUSSION: Adjuvant transsinuidal electrostimulation could thus enrich the conservative therapy of CRS. Further studies with larger collectives are desirable.

How vertical integration affects the quantity and cost of care for Medicare beneficiaries.

Health systems are employing physicians in growing numbers. The implications of this trend are poorly understood and controversial. We use rich data from the Centers for Medicare and Medicaid Services to examine the effects of a set of physician acquisitions by hospital systems on outpatient utilization and spending. We find that financial integration systematically produces economically large changes in the acquired physicians' behavior, but has less consistent effects at the acquiring system level.

Complementary and conventional medicine use among youth with recurrent headaches.

OBJECTIVE: To identify prevalence and patterns of complementary and alternative medicine (CAM) use among youth with recurrent headaches (HA) and evaluate associations with co-occurring health problems and limitations as well as with the use and expenditures for conventional medical care. METHODS: Variables were constructed for youth aged 10 to 17 by using linked data from the 2007 National Health Interview Survey and the 2008 Medical Expenditures Panel Survey. Bivariate, logistic, and 2-part regression analyses were used. RESULTS: Of the 10.6% of youth experiencing HA, 29.6% used CAM, rising to 41% for the many HA sufferers who also experienced difficulties with emotions, concentration, behavior, school attendance, or daily activities. Biologically based products (16.2%) and mind-body therapies (13.3%) were most commonly used, especially by the 86.4% of youth with HA experiencing at least 1 other chronic condition. Compared with non-CAM users, youth with HA who used CAM also had higher expenditures for and use of most types of conventional care. CONCLUSIONS: CAM use is most common among youth with HA experiencing multiple chronic conditions and difficulties in daily functioning. Associations among CAM use, multiple chronic conditions, and higher use of conventional care highlight the need for medical providers to routinely ask about CAM use to meet the complex health needs of their patients and facilitate the optimal integration of care. Research is needed to identify models for coordinating complementary and conventional care within a medical home and to understand the health benefits or risks associated with CAM use in conjunction with conventional treatments for patients with HA.

ADP-ribosylation factor-dependent phospholipase D2 activation is required for agonist-induced mu-opioid receptor endocytosis.

Agonist exposure of many G protein-coupled receptors induces a rapid receptor phosphorylation and uncoupling from G proteins. Resensitization of these desensitized receptors requires endocytosis and subsequent dephosphorylation. Using a yeast two-hybrid screen, the rat mu-opioid receptor (MOR1, also termed MOP) was found to be associated with phospholipase D2 (PLD2), a phospholipid-specific phosphodiesterase located in the plasma membrane, which has been implicated in the formation of endocytotic vesicles. Coimmunoprecipitation experiments in HEK293 cells coexpressing MOR1 and PLD2 confirmed that MOR1 constitutively interacts with PLD2. Treatment with the mu receptor agonist DAMGO ([d-Ala(2), Me Phe(4), Glyol(5)]enkephalin) led to an increase in PLD2 activity, whereas morphine, which does not induce MOR1 receptor internalization, failed to induce PLD2 activation. The DAMGO-mediated PLD2 activation was inhibited by brefeldin A, an inhibitor of ADP-ribosylation factor (ARF) but not by the protein kinase C (PKC) inhibitor calphostin C indicating that opioid receptor-mediated activation of PLD2 is ARF- but not PKC-dependent. Furthermore, heterologous stimulation of PLD2 by phorbol ester led to an accelerated internalization of the mu-opioid receptor after both DAMGO and morphine exposure. Conversely the inhibition of PLD2-mediated phosphatidic acid formation by 1-butanol or overexpression of a negative mutant of PLD2 prevented agonist-mediated endocytosis of MOR1. Together, these data suggest that PLD2 play a key role in the regulation of agonist-induced endocytosis of the mu-opioid receptor.