Long-Term Outcomes of Bleb Needling Following Primary Glaucoma Filtering Surgery in Primary Open Angle Glaucoma

Purpose: To determine the long-term success rate of bleb needling in a predominantly African American population and to identify factors associated with success. Methods: We conducted a retrospective, observational clinical study in patients with primary open angle glaucoma. Patients who underwent a primary trabeculectomy, with or without an express shunt placement, and then subsequently had a bleb needling procedure were selected for this study. Patients were followed every three months for a period of two years. Failure criteria included achieving an intraocular pressure (IOP) of greater than 20 mmHg or greater than 80% of the pre-needling value on two subsequent visits, an increase in the number of prescribed medications relative to pre-needling quantity, and the occurrence of other complications. Kaplan-Meier survival curves were used to calculate bleb needling success rates and variables associated with failure were analyzed using multivariate Cox regression analysis. Results: Seventy-four eyes from 71 patients were included in the study, with the majority of eyes from African Americans. The overall success rate at 12 months and two years was 28.1% and 14.3%, respectively. However, the complete success rate (completely weaned off of medications) was 12.7% and 5.1% at 12 months and 2 years, respectively. The most frequent reasons for failure included increased number of glaucoma medications (40%), surgical revision (31.7%), and IOP that exceeded threshold (21.7%). Conclusions: The two-year bleb needling success rate reported in our study is lower than that reported in other studies, possibly due to the increased severity of glaucoma in our patient population

Comparison of Zotarolimus-Eluting and Sirolimus-Eluting Stents in Patients With Native Coronary Artery Disease A Randomized Controlled Trial

ObjectivesThis trial examined the relative clinical efficacy, angiographic outcomes, and safety of zotarolimus-eluting coronary stents (ZES) with a phosphorylcholine polymer versus sirolimus-eluting stents (SES).BackgroundWhether a cobalt-based alloy stent coated with the novel antiproliferative agent, zotarolimus, and a phosphorylcholine polymer may provide similar angiographic and clinical benefit compared with SES is undetermined.MethodsA prospective, multicenter, 3:1 randomized trial was conducted to evaluate the safety and efficacy of ZES (n = 323) relative to SES (n = 113) in 436 patients undergoing elective percutaneous revascularization of de novo native coronary lesions with reference vessel diameters between 2.5 mm and 3.5 mm and lesion length ≥14 mm and ≤27 mm. The primary end point was 8-month angiographic in-segment late lumen loss.ResultsAngiographic in-segment late lumen loss was significantly higher among patients treated with ZES compared with SES (0.34 ± 0.44 mm vs. 0.13 ± 0.32 mm, respectively; p < 0.001). In-hospital major adverse cardiac events were significantly lower among patients treated with ZES (0.6% vs. 3.5%, p = 0.04). In-segment binary angiographic restenosis was also higher in the ZES cohort (11.7% vs. 4.3%, p = 0.04). Total (clinically and non-clinically driven) target lesion revascularization rates at 9 months were 9.8% and 3.5% for the ZES and SES groups, respectively (p = 0.04). However, neither clinically driven target lesion revascularization (6.3% zotarolimus vs. 3.5% sirolimus, p = 0.34) nor target vessel failure (12.0% zotarolimus vs. 11.5% sirolimus, p = 1.0) differed significantly.ConclusionsCompared with SES, treatment with a phosphorylcholine polymer-based ZES is associated with significantly higher late lumen loss and binary restenosis at 8-month angiographic follow-up.(The Endeavor III CR; http://clinicaltrials.gov/ct/show/NCT00265668?order=1?

Synthesis and in vivo evaluation of non-hepatotoxic acetaminophen analogs

A series of acetaminophen (APAP) analogs, 2-(1,1-dioxido-3-oxo-1,2-benzisothiazol-2(3H)-yl)-N-(4-hydroxyphenyl)alkanecarboxamides, bearing a heterocyclic moiety linked to the p-acylaminophenol fragment, were prepared in a general project to develop APAP analogs with modulated pharmacokinetic profiles. Unexpectedly, the products described maintained the in vivo analgesic profile, while the characteristic hepatotoxicity of APAP was consistently reduced. One of the products, 5a, was studied in vivo in comparison with APAP. Compound 5a displayed an analgesic efficacy comparable to that of APAP. A relatively high acute oral dose of 5a (6 mmol/kg) produced no measurable toxicity, whereas the equimolar dose of APAP increased transaminase activity, depleted hepatic and renal glutathione, and resulted in mortality. In human hepatocytes (HEPG-2) and in human primary cultures of normal liver cells, APAP, but not 5a, was associated with apoptotic cell death, Fas-ligand up-regulation, and CAR (constitutive androstane receptor) activation, contributing to a favorable safety profile of 5a as an orally delivered analgesic.MDA972-03-C-010 (Defense Advanced Research Programs Agency-DARPA)Neurobiotechnology Program of Louisian

Developments in Agricultural Soil Quality and Health: Reflections by the Research Committee on Soil Organic Matter Management

The North Central Education and Research Activity Committee (NCERA-59) was formed in 1952 to address how soil organic matter formation and management practices affect soil structure and productivity. It is in this capacity that we comment on the science supporting soil quality and associated soil health assessment for agricultural lands with the goal of hastening progress in this important field. Even though the suite of soil quality indicators being applied by U.S. soil health efforts closely mirrors the “minimum data set” we developed and recommended in the mid-1990s, we question whether the methods or means for their selection and development are sufficient to meet current and emerging soil health challenges. The rush to enshrine a standard suite of dated measures may be incompatible with longer-term goals. Legitimate study of soil health considers soil change accrued over years to decades that influence on- and off-site function. Tailoring of methods to local conditions is needed to effectively apply and interpret indicators for different soil resource regions and land uses. Adherence to a set suite of methods selected by subjective criteria should be avoided, particularly when we do not yet have adequate data or agreed upon interpretive frameworks for many so-called “Tier 1” biological indicators used in soil health assessment. While pooling data collected by producer-groups is one of the most exciting new trends in soil health, standardizing methods to meet broad inventory goals could compromise indicator use for site or application-specific problem solving. Changes in our nation’s research landscape are shifting responsibility for soil stewardship from national and state government backed entities to public-private partnerships. As a result, it is critical to ensure that the data needed to assess soil health are generated by reproducible methods selected through a transparent process, and that data are readily available for public and private sector use. Appropriate methods for engagement need to be applied by public-private research partnerships as they establish and expand coordinated research enterprises that can deliver fact-based interpretation of soil quality indicators within the type of normative soil health framework conceived by USDA over 20 years ago. We look to existing examples as we consider how to put soil health information into the hands of practitioners in a manner that protects soils’ services

Developments in Agricultural Soil Quality and Health: Reflections by the Research Committee on Soil Organic Matter Management

The North Central Education and Research Activity Committee (NCERA-59) was formed in 1952 to address how soil organic matter formation and management practices affect soil structure and productivity. It is in this capacity that we comment on the science supporting soil quality and associated soil health assessment for agricultural lands with the goal of hastening progress in this important field. Even though the suite of soil quality indicators being applied by U.S. soil health efforts closely mirrors the “minimum data set” we developed and recommended in the mid-1990s, we question whether the methods or means for their selection and development are sufficient to meet current and emerging soil health challenges. The rush to enshrine a standard suite of dated measures may be incompatible with longer-term goals. Legitimate study of soil health considers soil change accrued over years to decades that influence on- and off-site function. Tailoring of methods to local conditions is needed to effectively apply and interpret indicators for different soil resource regions and land uses. Adherence to a set suite of methods selected by subjective criteria should be avoided, particularly when we do not yet have adequate data or agreed upon interpretive frameworks for many so-called “Tier 1” biological indicators used in soil health assessment. While pooling data collected by producer-groups is one of the most exciting new trends in soil health, standardizing methods to meet broad inventory goals could compromise indicator use for site or application-specific problem solving. Changes in our nation’s research landscape are shifting responsibility for soil stewardship from national and state government backed entities to public-private partnerships. As a result, it is critical to ensure that the data needed to assess soil health are generated by reproducible methods selected through a transparent process, and that data are readily available for public and private sector use. Appropriate methods for engagement need to be applied by public-private research partnerships as they establish and expand coordinated research enterprises that can deliver fact-based interpretation of soil quality indicators within the type of normative soil health framework conceived by USDA over 20 years ago. We look to existing examples as we consider how to put soil health information into the hands of practitioners in a manner that protects soils’ services

Polymer-based paclitaxel-eluting stents reduce in-stent neointimal tissue proliferation A serial volumetric intravascular ultrasound analysis from the TAXUS-IV trial

ObjectivesThe aim of this study was to use serial volumetric intravascular ultrasound (IVUS) to evaluate the effects of polymer-based, paclitaxel-eluting stents on in-stent neointima formation and late incomplete stent apposition.BackgroundThe TAXUS-IV trial demonstrated that the slow-release, polymer-based, paclitaxel-eluting stent reduces angiographic restenosis and the need for repeat revascularization procedures. Serial IVUS studies reveal details of the pattern of vascular responses provoked by stent implantation that provide insight into device safety and efficacy.MethodsIn the TAXUS-IV trial, patients were randomized to the slow-release, polymer-based, paclitaxel-eluting TAXUS stent or a bare-metal EXPRESS stent (Boston Scientific Corp., Natick, Massachusetts). As part of a formal substudy, complete volumetric IVUS data were available in 170 patients, including 88 TAXUS patients and 82 controls, at implantation and at nine-month follow-up.ResultsNo baseline differences were present in the clinical characteristics or IVUS parameters between the control and TAXUS groups. At nine-month follow-up, IVUS lumen volumes were larger in the TAXUS group (123 ± 43 mm3vs. 104 ± 44 mm3, p = 0.005), due to a reduction in neointimal volume (18 ± 18 mm3vs. 41 ± 23 mm3, p < 0.001). Millimeter-by-millimeter analysis within the stent demonstrated uniform suppression of neointimal growth along the entire stent length. Late lumen loss was similar at the proximal edge of the stent between the two groups, and reduced with the TAXUS stent at the distal edge (p = 0.004). Incomplete stent apposition at nine months was observed in only 3.0% of control and 4.0% of TAXUS stents (p = 0.12).ConclusionsPolymer-based, paclitaxel-eluting TAXUS stents are effective in inhibiting neointimal tissue proliferation, and do not result in late incomplete stent apposition

Opportunities for organoids as new models of aging.

The biology of aging is challenging to study, particularly in humans. As a result, model organisms are used to approximate the physiological context of aging in humans. However, the best model organisms remain expensive and time-consuming to use. More importantly, they may not reflect directly on the process of aging in people. Human cell culture provides an alternative, but many functional signs of aging occur at the level of tissues rather than cells and are therefore not readily apparent in traditional cell culture models. Organoids have the potential to effectively balance between the strengths and weaknesses of traditional models of aging. They have sufficient complexity to capture relevant signs of aging at the molecular, cellular, and tissue levels, while presenting an experimentally tractable alternative to animal studies. Organoid systems have been developed to model many human tissues and diseases. Here we provide a perspective on the potential for organoids to serve as models for aging and describe how current organoid techniques could be applied to aging research