The P2X7 Receptor is an Important Regulator of Extracellular ATP Levels

Controlled ATP release has been demonstrated from many neuronal and non-neuronal cell types. Once released, extracellular ATP acts on cells in a paracrine manner via purinergic receptors. Considerable evidence now suggests that extracellular nucleotides, signaling via P2 receptors, play important roles in bone homeostasis modulating both osteoblast and osteoclast function. In this study, we demonstrate that mouse osteoclasts and their precursors constitutively release ATP into their extracellular environment. Levels were highest at day 2 (precursor cells), possibly reflecting the high number of red blood cells and accessory cells present. Mature osteoclasts constitutively released ATP in the range 0.05–0.5 pmol/ml/cell. Both osteoclasts and osteoblasts express mRNA and protein for the P2X7 receptor. We found that in osteoclasts, expression levels are fourfold higher in mature cells relative to precursors, whilst in osteoblasts expression remains relatively constant during differentiation. Selective antagonists (0.1–100 μM AZ10606120, A438079, and KN-62) were used to determine whether this release was mediated via P2X7 receptors. AZ10606120, A438079, and KN-62, at 0.1–10 μM, decreased ATP release by mature osteoclasts by up to 70, 60, and 80%, respectively. No differences in cell viability were observed. ATP release also occurs via vesicular exocytosis; inhibitors of this process (1–100 μM NEM or brefeldin A) had no effect on ATP release from osteoclasts. P2X7 receptor antagonists (0.1–10 μM) also decreased ATP release from primary rat osteoblasts by up to 80%. These data show that ATP release via the P2X7 receptor contributes to extracellular ATP levels in osteoclast and osteoblast cultures, suggesting an important additional role for this receptor in autocrine/paracrine purinergic signaling in bone

Effect of Faculty Development Activities on Dental Hygiene Faculty Perceptions of and Teaching About Motivational Interviewing: A Pilot Study

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153716/1/jddjde017048.pd

Ultrasonography for chairside evaluation of periodontal structures: A pilot study

BackgroundThe crestal bone level and soft tissue dimension are essential for periodontal diagnosis and phenotype determination; yet, existing measurement methods have limitations. The aim of this clinical study was to evaluate the correlation and accuracy of ultrasound in measuring periodontal dimensions, compared to direct clinical and cone- beam computed tomography (CBCT) methods.MethodsA 24- MHz ultrasound probe prototype, specifically designed for intraoral use, was employed. Periodontal soft tissue dimensions and crestal bone levels were measured at 40 teeth and 20 single missing tooth gaps from 20 patients scheduled to receive a dental implant surgery. The ultrasound images were interpreted by two calibrated examiners. Inter- rater agreement was calculated by using inter- rater correlation coefficient (ICC). Ultrasound readings were compared with direct clinical and CBCT readings by using ICC and Bland- Altman analysis.ResultsThe following six parameters were measured: 1) interdental papilla height (tooth), 2) mid- facial soft tissue height (tooth), 3) mucosal thickness (tooth), 4) soft tissue height (edentulous ridge), 5) mucosal thickness (edentulous ridge), and 6) crestal bone level (tooth). Intra- examiner calibrations were exercised to achieve an agreement of at least 0.8. ICC between the two readers ranged from 0.482 to 0.881. ICC between ultrasound and direct readings ranged from 0.667 to 0.957. The mean difference in mucosal thickness (tooth) between the ultrasound and direct readings was - 0.015 mm (95% CI: - 0.655 to 0.624 mm) without statistical significance. ICC between ultrasound and CBCT ranged from 0.654 to 0.849 among the measured parameters. The mean differences between ultrasound and CBCT range from - 0.213 to 0.455 mm, without statistical significance.ConclusionUltrasonic imaging can be valuable for accurate and real- time periodontal diagnosis without concerns about ionizing radiation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156207/2/jper10483_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156207/1/jper10483.pd

Cost Benefit Analysis of Idaho’s Fit and Fall Proof Program

Falls are common among the elderly population. Almost 30% of Idahoans aged 65+ fall at least one time per year (Bergen, Stevens, & Burns, 2016). Falls are a significant source of morbidity, mortality, and healthcare expense. Fall-related injuries often result in expensive hospitalizations with progression into costly long-term care facilities (CDC, 2015). In Idaho, estimated fall-related medical costs are estimated at $253 million annually (CDC, 2016; Mirel & Carper, 2014). Fit and Fall ProofTM (FFP), is a fall prevention program serving approximately 2500 community dwelling seniors throughout the state of Idaho. It is an exercise program led by peer volunteer instructors incorporating evidence-based methods of reducing the risk of falls. In addition to fall prevention, exercise programs such as FFP have well-established positive benefits on mental health, obesity rates, diabetes, and cardio-vascular health. All of these health benefits translate to savings in healthcare expense. This cost benefit analysis (CBA) of FFP estimates savings in total direct medical costs of participants, and also calculates the portion of savings due to averted falls and averted cases of major depressive disorder (MDD). The CBA adopts a societal perspective, incorporating all sources of funding, both federal and state. In a similar way, all savings in direct medical costs are included in the analysis whether these cost-savings accrue to Medicare, Medicaid, private insurers, or FFP participants themselves. Due to the community-based nature of the intervention and privacy considerations, there is no information available on falls and related medical costs among FFP participants. Therefore, this CBA relies on modeled data obtained from other studies; however, conservative estimates of program efficacy and base fall incidence rates were employed. All costs were adjusted for medical inflation to 2016 dollars

Extracellular ATP released by osteoblasts is a key local inhibitor of bone mineralisation

Previous studies have shown that exogenous ATP (>1µM) prevents bone formation in vitro by blocking mineralisation of the collagenous matrix. This effect is thought to be mediated via both P2 receptor-dependent pathways and a receptor-independent mechanism (hydrolysis of ATP to produce the mineralisation inhibitor pyrophosphate, PPi). Osteoblasts are also known to release ATP constitutively. To determine whether this endogenous ATP might exert significant biological effects, bone-forming primary rat osteoblasts were cultured with 0.5-2.5U/ml apyrase (which sequentially hydrolyses ATP to ADP to AMP + 2Pi). Addition of 0.5U/ml apyrase to osteoblast culture medium degraded extracellular ATP to <1% of control levels within 2 minutes; continuous exposure to apyrase maintained this inhibition for up to 14 days. Apyrase treatment for the first 72 hours of culture caused small decreases (≤25%) in osteoblast number, suggesting a role for endogenous ATP in stimulating cell proliferation. Continuous apyrase treatment for 14 days (≥0.5U/ml) increased mineralisation of bone nodules by up to 3-fold. Increases in bone mineralisation were also seen when osteoblasts were cultured with the ATP release inhibitors, NEM and brefeldin A, as well as with P2X1 and P2X7 receptor antagonists. Apyrase decreased alkaline phosphatase (TNAP) activity by up to 60%, whilst increasing the activity of the PPi-generating ecto-nucleotide pyrophosphatase/phosphodiesterases (NPPs) up to 2.7-fold. Both collagen production and adipocyte formation were unaffected. These data suggest that nucleotides released by osteoblasts in bone could act locally, via multiple mechanisms, to limit mineralisation

LSST Science Book, Version 2.0

A survey that can cover the sky in optical bands over wide fields to faint magnitudes with a fast cadence will enable many of the exciting science opportunities of the next decade. The Large Synoptic Survey Telescope (LSST) will have an effective aperture of 6.7 meters and an imaging camera with field of view of 9.6 deg^2, and will be devoted to a ten-year imaging survey over 20,000 deg^2 south of +15 deg. Each pointing will be imaged 2000 times with fifteen second exposures in six broad bands from 0.35 to 1.1 microns, to a total point-source depth of r~27.5. The LSST Science Book describes the basic parameters of the LSST hardware, software, and observing plans. The book discusses educational and outreach opportunities, then goes on to describe a broad range of science that LSST will revolutionize: mapping the inner and outer Solar System, stellar populations in the Milky Way and nearby galaxies, the structure of the Milky Way disk and halo and other objects in the Local Volume, transient and variable objects both at low and high redshift, and the properties of normal and active galaxies at low and high redshift. It then turns to far-field cosmological topics, exploring properties of supernovae to z~1, strong and weak lensing, the large-scale distribution of galaxies and baryon oscillations, and how these different probes may be combined to constrain cosmological models and the physics of dark energy.Comment: 596 pages. Also available at full resolution at http://www.lsst.org/lsst/sciboo

2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: Executive summary: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines

[Extract] Top 10 Take-Home Messages for the Primary Prevention of Cardiovascular Disease 1. The most important way to prevent atherosclerotic vascular disease, heart failure, and atrial fibrillation is to promote a healthy lifestyle throughout life. 2. A team-based care approach is an effective strategy for the prevention of cardiovascular disease. Clinicians should evaluate the social determinants of health that affect individuals to inform treatment decisions. 3. Adults who are 40 to 75 years of age and are being evaluated for cardiovascular disease prevention should undergo 10-year atherosclerotic cardiovascular disease (ASCVD) risk estimation and have a clinician–patient risk discussion before starting on pharmacological therapy, such as antihypertensive therapy, a statin, or aspirin. In addition, assessing for other risk-enhancing factors can help guide decisions about preventive interventions in select individuals, as can coronary artery calcium scanning. 4. All adults should consume a healthy diet that emphasizes the intake of vegetables, fruits, nuts, whole grains, lean vegetable or animal protein, and fish and minimizes the intake of trans fats, red meat and processed red meats, refined carbohydrates, and sweetened beverages. For adults with overweight and obesity, counseling and caloric restriction are recommended for achieving and maintaining weight loss. 5. Adults should engage in at least 150 minutes per week of accumulated moderate-intensity physical activity or 75 minutes per week of vigorous-intensity physical activity. 6. For adults with type 2 diabetes mellitus, lifestyle changes, such as improving dietary habits and achieving exercise recommendations, are crucial. If medication is indicated, metformin is first-line therapy, followed by consideration of a sodium-glucose cotransporter 2 inhibitor or a glucagon-like peptide-1 receptor agonist. 7. All adults should be assessed at every healthcare visit for tobacco use, and those who use tobacco should be assisted and strongly advised to quit. 8. Aspirin should be used infrequently in the routine primary prevention of ASCVD because of lack of net benefit. 9. Statin therapy is first-line treatment for primary prevention of ASCVD in patients with elevated low-density lipoprotein cholesterol levels (≥190 mg/dL), those with diabetes mellitus, who are 40 to 75 years of age, and those determined to be at sufficient ASCVD risk after a clinician–patient risk discussion. 10. Nonpharmacological interventions are recommended for all adults with elevated blood pressure or hypertension. For those requiring pharmacological therapy, the target blood pressure should generally be <130/80 mm Hg

History, epidemiology and regional diversities of urolithiasis

Archeological findings give profound evidence that humans have suffered from kidney and bladder stones for centuries. Bladder stones were more prevalent during older ages, but kidney stones became more prevalent during the past 100 years, at least in the more developed countries. Also, treatment options and conservative measures, as well as ‘surgical’ interventions have also been known for a long time. Our current preventive measures are definitively comparable to those of our predecessors. Stone removal, first lithotomy for bladder stones, followed by transurethral methods, was definitively painful and had severe side effects. Then, as now, the incidence of urolithiasis in a given population was dependent on the geographic area, racial distribution, socio-economic status and dietary habits. Changes in the latter factors during the past decades have affected the incidence and also the site and chemical composition of calculi, with calcium oxalate stones being now the most prevalent. Major differences in frequency of other constituents, particularly uric acid and struvite, reflect eating habits and infection risk factors specific to certain populations. Extensive epidemiological observations have emphasized the importance of nutritional factors in the pathogenesis of urolithiasis, and specific dietary advice is, nowadays, often the most appropriate for prevention and treatment of urolithiasis