Pulmonary alveolar proteinosis: a rare pulmonary toxicity of sirolimus.

Transpl Int. 2007 Mar;20(3):291-6. Pulmonary alveolar proteinosis: a rare pulmonary toxicity of sirolimus. Pedroso SL, Martins LS, Sousa S, Reis A, Dias L, Henriques AC, Sarmento AM, Cabrita A. Nephrology Department, Hospital Geral de Santo António, Porto, Portugal. [email protected] Abstract The aim of our paper is to describe an unusual pulmonary toxicity of sirolimus (SRL) in a kidney transplant recipient. We present a 34-year-old woman with a second renal transplantation, complicated with steroid-resistant acute rejection and chronic allograft dysfunction. Two years after initiating SRL, she presented complaints of progressive dyspnoea, nonproductive cough, chest pain and low-grade fever of 1 month duration. She had chronic allograft nephropathy and slight elevation of lactic dehydrogenase levels. After exclusion of common reasons of this condition, a computed tomography (CT) of the thorax and bronchoscopy was performed, revealing ground-glass opacification with polygonal shapes on CT and an opaque appearance with numerous macrophages on bronchoalveolar lavage. The alveolar macrophages stained positive by Periodic acid-Schiff. Diagnosis of pulmonary alveolar proteinosis (PAP) was made and drug-induced toxicity was suspected. SRL was withdrawn with marked improvement in the patients' clinical and radiological status. PAP resolved within 3 months without further therapy. PAP is a very rare complication of SRL therapy with only a few cases described. Withdrawal of SRL with conversion to another immunosuppressant seems to be an appropriate procedure in this condition. PMID: 17291222 [PubMed - indexed for MEDLIN

Controlled release strategies for bone, cartilage, and osteochondral engineering: part I: recapitulation of native tissue healing and variables for the design of delivery systems

The potential of growth factors to stimulate tissue healing through the enhancement of cell proliferation, migration, and differentiation is undeniable. However, critical parameters on the design of adequate carriers, such as uncontrolled spatiotemporal presence of bioactive factors, inadequate release profiles, and supraphysiological dosages of growth factors, have impaired the translation of these systems onto clinical practice. This review describes the healing cascades for bone, cartilage, and osteochondral interface, highlighting the role of specific growth factors for triggering the reactions leading to tissue regeneration. Critical criteria on the design of carriersfor controlled release of bioactive factors are also reported, focusing on the need to provide a spatiotemporal control over the delivery and presentation of these molecules.The authors thank Fundacao para a Ciencia e Tecnologia for V.E.Santo's PhD grant (SFRH/BD/39486/2007). This work was carried out under the scope of the European FP7 Project Find and Bind (NMP4-SL-2009-229292) and Project MIT/ECE/0047/2009

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Qualitative characteristics of meat from confined crossbred heifers fed with lipid sources

Lipids have been used in ruminant feed to replace high amounts of grain for increasing the diet energy density, performance and meat quality. This study evaluated the qualitative characteristics of meat from feedlot heifers fed with sources of lipid supplements. Twenty-one crossbred heifers (1/4Nelore × 1/4Santa Gertrudis × 1/2Braunvieh) were used. Each heifer received 60 % forage with a base of corn silage and 40 % concentrate, resulting in 5.8 % lipid content in the total diet. The following sources of lipids were used: soybeans, protected fat and soybean oil. There were no differences on physical characteristics of meat samples from heifers fed with the lipid sources. Soybeans increased the concentration of linoleic acid, content of polyunsaturated fatty acid and activity of the Δ9-desaturase C16 enzyme in the Longissimus muscle. The use of soybean oil in the diet increased the oleic acid, monounsaturated fatty acid, total cis- and trans-fatty acids (C18:0) and the activity of the Δ9-desaturase C16 enzyme in the subcutaneous fat. Diets with soybean grain had greater deposition of linoleic and linolenic acids than diets with fat protected and greater presence of these essential fatty acids are associated to a better composition and meat quality

Aberrant Expression of Cell Cycle Regulator 14-3-3-σ and E-Cadherin in a Metastatic Cholangiocarcinoma in a Vervet Monkey (Chlorocebus pygerythrus).

We present a unique case of metastatic cholangiocarcinoma with concurrent abdominal cestodiasis in an African green monkey (Chlorocebus pygerythrus) that presented with respiratory insufficiency and abdominal discomfort. There were multiple white-grey masses in the liver and colonic serosa alongside intra-abdominal parasitic cysts. Histopathologically, the liver masses were composed of poorly-differentiated epithelial cells that formed densely cellular solid areas and trabeculae. The neoplastic cells were strongly immunopositive for CK7 but negative for Hep-Par1 antigen, which confirmed a diagnosis of cholangiocarcinoma. Interestingly, there was strong and diffuse neoexpression in the tumour of the cell cycle regulator 14-3-3σ, which is not constitutively expressed in normal liver. There was aberrantly strong expression of E-cadherin, a key cell-cell adhesion protein, in neoplastic cells with evidence of cytoplasmic internalization. This is the first immunohistochemical analysis of 14-3-3σ and E-cadherin in a liver neoplasm in an animal species and the use of these markers requires further investigation in animal liver neoplasms. [Abstract copyright: Copyright © 2020 Elsevier Ltd. All rights reserved.

How many bird and mammal extinctions has recent conservation action prevented?

Aichi Target 12 of the Convention on Biological Diversity (CBD) aims to ‘prevent extinctions of known threatened species’. To measure its success, we used a Delphi expert elicitation method to estimate the number of bird and mammal species whose extinctions were prevented by conservation action in 1993 - 2020 (the lifetime of the CBD) and 2010 - 2020 (the timing of Aichi Target 12). We found that conservation prevented 21–32 bird and 7–16 mammal extinctions since 1993, and 9–18 bird and 2–7 mammal extinctions since 2010. Many remain highly threatened, and may still become extinct in the near future. Nonetheless, given that ten bird and five mammal species did go extinct (or are strongly suspected to) since 1993, extinction rates would have been 2.9–4.2 times greater without conservation action. While policy commitments have fostered significant conservation achievements, future biodiversity action needs to be scaled up to avert additional extinctions