Patterned expression of neurotrophic factors and receptors in human limbal and corneal regions

PURPOSE: To evaluate the expression patterns of neurotrophic factors (NTFs) and their receptors in the human cornea with the intention of exploring the role of NTFs in maintaining corneal epithelial stem cells in the limbus. METHODS: Fresh human corneoscleral tissues were prepared for frozen sections. Immunofluorescent staining was performed with primary antibodies against six members of three NTF families and their six receptors. To confirm the specificity of NTF primary antibodies, neutralization experiments with their corresponding peptides and western blot analysis were performed. RESULTS: Based on spatial and differential immuno-localization, three patterns of NTF expression were potentially involved in epithelial-mesenchymal interaction on the ocular surface: (1) the epithelial type: nerve growth factor (NGF) and glial cell-derived neurotrophic factor (GDNF); (2) the paracrine type: neurotrophin (NT)-3 and NT-4/5; and (3) the reciprocal type: brain-derived neurotrophic factor (BDNF). The stem cell-enriched basal cells of the limbal epithelium expressed three unique staining patterns for NTFs: (1) exclusively positive for NGF, GDNF, and their corresponding receptors, TrkA and GDNF family receptor alpha (GFR)-1; (2) relatively high levels of BDNF; and (3) negative for NT-3 and NT-4. Additionally, the neurotrophin common low-affinity receptor, p75NTR, was mainly expressed by the basal layer of the entire corneal and limbal epithelia, and TrkB and TrkC were evenly expressed by the entire corneal and limbal epithelia. BDNF, p75NTR, TrkB, and TrkC are also abundantly expressed by limbal stroma cells. No specific immunoreactivity to ciliary neurotrophic factor (CNTF) and its receptor, CNTFR, was detected in cornea tissue in situ. CONCLUSIONS: Our findings revealed patterned expression of NTFs and their receptors in the human ocular surface, suggesting that they may play a vital role in maintaining corneal epithelial stem cells in the limbus. NGF, GDNF, GFR-1, TrkA, and BDNF may serve as new limbal basal cell markers defining the corneal epithelial stem cell phenotype.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000250807800002&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Biochemistry & Molecular BiologyOphthalmologySCI(E)42ARTICLE217-191934-19411

Prevalence of chronic kidney disease in the community in the United Kingdom in OxRen, a population-based cohort study

Background: Chronic kidney disease (CKD) is a largely asymptomatic condition of diminished renal function, which may not be detected until advanced stages without screening. Aim: To establish undiagnosed and overall CKD prevalence using a cross-sectional analysis. Design and Setting: Longitudinal cohort study in UK primary care. Method: Participants aged ≥60 years were invited to attend CKD screening visits to determine whether they had reduced renal function (estimated glomerular filtration rate [eGFR] Results: A total of 3207 participants were recruited and 861 attended the baseline assessment. The CKD cohort consisted of 327 people with existing CKD, 257 people with CKD diagnosed through screening (CKD prevalence of 18.2%, 95% confidence interval [CI] = 16.9 to 19.6), and 277 with borderline/transient decreased renal function. In the CKD cohort, 54.4% were female, mean standard deviation (SD) age was 74.0 (SD 6.9) years, and mean eGFR was 58.0 (SD 18.4) ml/min/1.73 m2. Of the 584 with confirmed CKD, 44.0% were diagnosed through screening. Over half of the CKD cohort (51.9%, 447/861) fell into CKD stages 3–5 at their baseline assessment, giving an overall prevalence of CKD stages 3–5 of 13.9% (95% CI = 12.8 to 15.1). More people had reduced eGFR using the Modification of Diet in Renal Disease (MDRD) equation than with CKD Epidemiology Collaboration (CKD-EPI) equation in the 60–75-year age group and more had reduced eGFR using CKD-EPI in the ≥80-year age group. Conclusion: This study found that around 44.0% of people living with CKD are undiagnosed without screening, and prevalence of CKD stages 1–5 was 18.2% in participants aged >60 years. Follow-up will provide data on annual incidence, rate of CKD progression, determinants of rapid progression, and predictors of cardiovascular events.</p

Evidence for changes in stratospheric transport and mixing over the past three decades based on multiple data sets and tropical leaky pipe analysis

Variability in the strength of the stratospheric Lagrangian mean meridional or Brewer-Dobson circulation and horizontal mixing into the tropics over the past three decades are examined using observations of stratospheric mean age of air and ozone. We use a simple representation of the stratosphere, the tropical leaky pipe (TLP) model, guided by mean meridional circulation and horizontal mixing changes in several reanalyses data sets and chemistry climate model (CCM) simulations, to help elucidate reasons for the observed changes in stratospheric mean age and ozone. We find that the TLP model is able to accurately simulate multiyear variability in ozone following recent major volcanic eruptions and the early 2000s sea surface temperature changes, as well as the lasting impact on mean age of relatively short-term circulation perturbations. We also find that the best quantitative agreement with the observed mean age and ozone trends over the past three decades is found assuming a small strengthening of the mean circulation in the lower stratosphere, a moderate weakening of the mean circulation in the middle and upper stratosphere, and a moderate increase in the horizontal mixing into the tropics. The mean age trends are strongly sensitive to trends in the horizontal mixing into the tropics, and the uncertainty in the mixing trends causes uncertainty in the mean circulation trends. Comparisons of the mean circulation and mixing changes suggested by the measurements with those from a recent suite of CCM runs reveal significant differences that may have important implications on the accurate simulation of future stratospheric climate

VIDEO: Session 1: Introduction and Welcome, and Keynote Address: Challenges and Responses

VIDEO (47:37): SESSION 1: Introduction and Welcome, and Keynote Address: Challenges and Responses Introduction: Lakshman Guruswamy, Director of the Center for Energy and Environmental Security (CEES), Professor of Law, University of Colorado at Boulder Welcome: David Getches, Dean, School of Law, University of Colorado at Boulder Introduction of Keynote Speaker: Doug Vilsack, CEO, Elephant Energy Keynote Address: Challenges and Responses: Dr. Dan Shine, Senior Adviser, Office of Science and Technology, U.S. Agency for International Development (USAID

VIDEO: Session 1: Introduction and Welcome, and Keynote Address: Challenges and Responses

VIDEO (47:37): SESSION 1: Introduction and Welcome, and Keynote Address: Challenges and Responses Introduction: Lakshman Guruswamy, Director of the Center for Energy and Environmental Security (CEES), Professor of Law, University of Colorado at Boulder Welcome: David Getches, Dean, School of Law, University of Colorado at Boulder Introduction of Keynote Speaker: Doug Vilsack, CEO, Elephant Energy Keynote Address: Challenges and Responses: Dr. Dan Shine, Senior Adviser, Office of Science and Technology, U.S. Agency for International Development (USAID

Reduced kidney function at presentation in unselected acute emergency medical admissions:incidence, outcome and associated factors

We sought to assess the impact of renal impairment on acute medical admissions and to identify potential contributory factors to admissions involving renal impairment at presentation. In a prospective cohort study, 29.5% of all acute medical emergency admissions had an eGFR < 60 ml/min/1.73m2 at presentation. Of these, 19.9 % had definite chronic kidney disease and 8.4 % had definite acute kidney injury. Detailed analysis of a random subset of patients with an eGFR <60ml/min/1.73m2 at presentation demonstrated that the major reasons for admission included falls, dehydration and fluid overload. 46% were on diuretics and 53% were on an ACEI or ARB or both. Gastrointestinal disturbance and recent medication changes were common and diuretic use persisted even with diarrhoea or vomiting