Afferent activity to necklace glomeruli is dependent on external stimuli

<p>Abstract</p> <p>Background</p> <p>The main olfactory epithelium (MOE) is a complex organ containing several functionally distinct subpopulations of sensory neurons. One such subpopulation is distinguished by its expression of the guanylyl cyclase GC-D. The axons of GC-D-expressing (GC-D+) neurons innervate 9–15 "necklace" glomeruli encircling the caudal main olfactory bulb (MOB). Chemosensory stimuli for GC-D+ neurons include two natriuretic peptides, uroguanylin and guanylin, and CO₂. However, the biologically-relevant source of these chemostimuli is unclear: uroguanylin is both excreted in urine, a rich source of olfactory stimuli for rodents, and expressed in human nasal epithelium; CO₂is present in both inspired and expired air.</p> <p>Findings</p> <p>To determine whether the principal source of chemostimuli for GC-D+ neurons is external or internal to the nose, we assessed the consequences of removing external chemostimuli for afferent activity to the necklace glomeruli. To do so, we performed unilateral naris occlusions in <it>Gucy2d-Mapt-lacZ </it>^+/-mice [which express a β-galactosidase (β-gal) reporter specifically in GC-D+ neurons] followed by immunohistochemistry for β-gal and a glomerular marker of afferent activity, tyrosine hydroxylase (TH). We observed a dramatic decrease in TH immunostaining, consistent with reduced or absent afferent activity, in both necklace and non-necklace glomeruli ipsilateral to the occluded naris.</p> <p>Conclusion</p> <p>Like other MOB glomeruli, necklace glomeruli exhibit a large decrease in afferent activity upon removal of external stimuli. Thus, we conclude that activity in GC-D+ neurons, which specifically innervate necklace glomeruli, is not dependent on internal stimuli. Instead, GC-D+ neurons, like other OSNs in the MOE, primarily sense the external world.</p

MR Spectroscopic Imaging of Peripheral Zone in Prostate Cancer Using a 3T MRI Scanner: Endorectal versus External Phased Array Coils.

Magnetic resonance spectroscopic imaging (MRSI) detects alterations in major prostate metabolites, such as citrate (Cit), creatine (Cr), and choline (Ch). We evaluated the sensitivity and accuracy of three-dimensional MRSI of prostate using an endorectal compared to an external phased array "receive" coil on a 3T MRI scanner. Eighteen patients with prostate cancer (PCa) who underwent endorectal MR imaging and proton (1H) MRSI were included in this study. Immediately after the endorectal MRSI scan, the PCa patients were scanned with the external phased array coil. The endorectal coil-detected metabolite ratio [(Ch+Cr)/Cit] was significantly higher in cancer locations (1.667 ± 0.663) compared to non-cancer locations (0.978 ± 0.420) (P &lt; 0.001). Similarly, for the external phased array, the ratio was significantly higher in cancer locations (1.070 ± 0.525) compared to non-cancer locations (0.521 ± 0.310) (P &lt; 0.001). The sensitivity and accuracy of cancer detection were 81% and 78% using the endorectal 'receive' coil, and 69% and 75%, respectively using the external phased array 'receive' coil

Correlation of Gleason Scores with Diffusion-Weighted Imaging Findings of Prostate Cancer

The purpose of our study was to compare the apparent diffusion coefficient (ADC) derived from diffusion-weighted imaging (DWI) of prostate cancer (PCa) patients with three classes of pathological Gleason scores (GS). Patients whose GS met these criteria (GS 3 + 3, GS 3 + 4, and GS 4 + 3) were included in this study. The DWI was performed using b values of 0, 50, and 400 s/mm2 in 44 patients using an endorectal coil on a 1.5T MRI scanner. The apparent diffusion coefficient (ADC) values were calculated from the DWI data of patients with three different Gleason scores. In patients with a high-grade Gleason score (4 + 3), the ADC values were lower in the peripheral gland tissue, pathologically determined as tumor compared to low grade (3 + 3 and 3 + 4). The mean and standard deviation of the ADC values for patients with GS 3 + 3, GS 3 + 4, and GS 4 + 3 were 1.135 ± 0.119, 0.976 ± 0.103 and 0.831 ± 0.087 mm2/sec. The ADC values were statistically significant (P < 0.05) between the three different scores with a trend of decreasing ADC values with increasing Gleason scores by one-way ANOVA method. This study shows that the DWI-derived ADC values may help differentiate aggressive from low-grade PCa

Psoriasis Is Common, Carries a Substantial Burden Even When Not Extensive, and Is Associated with Widespread Treatment Dissatisfaction

The impact of psoriasis on quality of life has been studied in select patient populations. Population-based data detailing the distribution of extent of disease, associated problems in everyday life, and treatment satisfaction for the US population have been lacking. Our population-based survey indicates that approximately 4.5 million adults have been diagnosed as having psoriasis. Most (59%) have little or no involvement, but 650,000 adults have at least three palms of body surface involved and more than 1,000,000 indicate substantial dissatisfaction with their treatment. Only 5% of patients (56,000) who report severe dissatisfaction with current therapy have extensive disease (10 palms). Many individuals with little psoriasis at the time of interview considered the disease to be a large problem in everyday life

Modeling Analysis of Primary Controls on Net Ecosystem Productivity of Seven Boreal and Temperate Coniferous Forests Across a Continental Transect

Process-based models are effective tools to synthesize and/or extrapolate measured carbon (C) exchanges from individual sites to large scales. In this study, we used a C- and nitrogen (N)-cycle coupled ecosystem model named CN-CLASS (Carbon Nitrogen-Canadian Land Surface Scheme) to study the role of primary climatic controls and site-specific C stocks on the net ecosystem productivity (NEP) of seven intermediate-aged to mature coniferous forest sites across an east–west continental transect in Canada. The model was parameterized using a common set of parameters, except for two used in empirical canopy conductance–assimilation, and leaf area–sapwood relationships, and then validated using observed eddy covariance flux data. Leaf Rubisco-N dynamics that are associated with soil–plant N cycling, and depend on canopy temperature, enabled the model to simulate site-specific gross ecosystem productivity (GEP) reasonably well for all seven sites. Overall GEP simulations had relatively smaller differences compared with observations vs. ecosystem respiration (RE), which was the sum of many plant and soil components with larger variability and/or uncertainty associated with them. Both observed and simulated data showed that, on an annual basis, boreal forest sites were either carbon-neutral or a weak C sink, ranging from 30 to 180 g C m−2 yr−1; while temperate forests were either a medium or strong C sink, ranging from 150 to 500 g C m−2 yr−1, depending on forest age and climatic regime. Model sensitivity tests illustrated that air temperature, among climate variables, and aboveground biomass, among major C stocks, were dominant factors impacting annual NEP. Vegetation biomass effects on annual GEP, RE and NEP showed similar patterns of variability at four boreal and three temperate forests. Air temperature showed different impacts on GEP and RE, and the response varied considerably from site to site. Higher solar radiation enhanced GEP, while precipitation differences had a minor effect. Magnitude of forest litter content and soil organic matter (SOM) affected RE. SOM also affected GEP, but only at low levels of SOM, because of low N mineralization that limited soil nutrient (N) availability. The results of this study will help to evaluate the impact of future climatic changes and/or forest C stock variations on C uptake and loss in forest ecosystems growing in diverse environments.Earth and Planetary Science

Risk of major cardiovascular events in patients with psoriatic arthritis, psoriasis and rheumatoid arthritis: a population-based cohort study.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.We aimed to quantify the risk of major adverse cardiovascular events (MACE) among patients with psoriatic arthritis (PsA), rheumatoid arthritis (RA) and psoriasis without known PsA compared with the general population after adjusting for traditional cardiovascular risk factors.A population-based longitudinal cohort study from 1994 to 2010 was performed in The Health Improvement Network (THIN), a primary care medical record database in the UK. Patients aged 18-89 years of age with PsA, RA or psoriasis were included. Up to 10 unexposed controls matched on practice and index date were selected for each patient with PsA. Outcomes included cardiovascular death, myocardial infarction, cerebrovascular accidents and the composite outcome (MACE). Cox proportional hazards models were used to calculate the HRs for each outcome adjusted for traditional risk factors. A priori, we hypothesised an interaction between disease status and disease-modifying antirheumatic drug (DMARD) use.Patients with PsA (N=8706), RA (N=41 752), psoriasis (N=138 424) and unexposed controls (N=81 573) were identified. After adjustment for traditional risk factors, the risk of MACE was higher in patients with PsA not prescribed a DMARD (HR 1.24, 95% CI 1.03 to 1.49), patients with RA (No DMARD: HR 1.39, 95% CI 1.28 to 1.50, DMARD: HR 1.58, 95% CI 1.46 to 1.70), patients with psoriasis not prescribed a DMARD (HR 1.08, 95% CI 1.02 to 1.15) and patients with severe psoriasis (DMARD users: HR 1.42, 95% CI 1.17 to 1.73).Cardiovascular risk should be addressed with all patients affected by psoriasis, PsA or RA.American College of Rheumatology R01HL089744 K24AR064310 Clinical and Translational Science Award at the University of Pennsylvania from the National Center for Research Resources 8UL1TR000003 American College of Rheumatology Research and Education Foundation NIH K23AR063764 Doris Duke Charitable Foundation Center for Clinical Epidemiology and Biostatistics Icelandic Research Fund 120433021 R01AG025152 K23HL097151-0

Modeled Health and Economic Impact of Team-Based Care for Hypertension

IntroductionTeam-based interventions for hypertension care have been widely studied and shown effective in improving hypertension outcomes. Few studies have evaluated long-term effects of these interventions; none have assessed broad-scale implementation. This study estimates the prospective health, economic, and budgetary impact of universal adoption of a team-based care intervention model that targets people with treated but uncontrolled hypertension in the U.S.MethodsAnalysis was conducted in 2014−2015 using a microsimulation model, constructed with various data sources from 1948 to 2014, designed to evaluate prospective cardiovascular disease (CVD)−related interventions in the U.S. population. Ten-year primary outcomes included prevalence of uncontrolled hypertension; incident myocardial infarction, stroke, CVD events, and CVD-related mortality; intervention and net medical costs by payer; productivity; and quality-adjusted life years.ResultsAbout 4.7 million (13%) fewer people with uncontrolled hypertension and 638,000 prevented cardiovascular events would be expected over 10 years. Assuming $525 per enrollee, implementation would cost payers$22.9 billion, but $25.3 billion would be saved in averted medical costs. Estimated net cost savings for Medicare approached$5.8 billion. Net costs were especially sensitive to intervention costs, with break-even thresholds of $300 (private),$450 (Medicaid), and $750 (Medicare).ConclusionsNationwide adoption of team-based care for uncontrolled hypertension could have sizable effects in reducing CVD burden. Based on the study’s assumptions, the policy would be cost saving from the perspective of Medicare and may prove to be cost effective from other payers’ perspectives. Expected net cost savings for Medicare would more than offset expected net costs for all other insurers

Get screened: a pragmatic randomized controlled trial to increase mammography and colorectal cancer screening in a large, safety net practice

Abstract Background Most randomized controlled trials of interventions designed to promote cancer screening, particularly those targeting poor and minority patients, enroll selected patients. Relatively little is known about the benefits of these interventions among unselected patients. Methods/Design "Get Screened" is an American Cancer Society-sponsored randomized controlled trial designed to promote mammography and colorectal cancer screening in a primary care practice serving low-income patients. Eligible patients who are past due for mammography or colorectal cancer screening are entered into a tracking registry and randomly assigned to early or delayed intervention. This 6-month intervention is multimodal, involving patient prompts, clinician prompts, and outreach. At the time of the patient visit, eligible patients receive a low-literacy patient education tool. At the same time, clinicians receive a prompt to remind them to order the test and, when appropriate, a tool designed to simplify colorectal cancer screening decision-making. Patient outreach consists of personalized letters, automated telephone reminders, assistance with scheduling, and linkage of uninsured patients to the local National Breast and Cervical Cancer Early Detection program. Interventions are repeated for patients who fail to respond to early interventions. We will compare rates of screening between randomized groups, as well as planned secondary analyses of minority patients and uninsured patients. Data from the pilot phase show that this multimodal intervention triples rates of cancer screening (adjusted odds ratio 3.63; 95% CI 2.35 - 5.61). Discussion This study protocol is designed to assess a multimodal approach to promotion of breast and colorectal cancer screening among underserved patients. We hypothesize that a multimodal approach will significantly improve cancer screening rates. The trial was registered at Clinical Trials.gov NCT00818857http://deepblue.lib.umich.edu/bitstream/2027.42/78264/1/1472-6963-10-280.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78264/2/1472-6963-10-280.pdfPeer Reviewe

Household Tobacco Smoke and Admission Weight Predict Severe Bronchiolitis in Infants Independent of Deprivation: Prospective Cohort Study

To examine demographic, environmental and clinical factors associated with severe bronchiolitis in infants admitted to hospital and quantify the independent effects of these factors