Integrated Optical Coherence Tomography and Optical Coherence Microscopy Imaging of Ex Vivo Human Renal Tissues

available in PMC 2012 June 04Materials and Methods A total of 35 renal specimens from 19 patients, consisting of 12 normal tissues and 23 tumors (16 clear cell renal cell carcinomas, 5 papillary renal cell carcinomas and 2 oncocytomas) were imaged ex vivo after surgical resection. Optical coherence tomography and optical coherence microscopy images were compared to corresponding hematoxylin and eosin histology to identify characteristic features of normal and pathological renal tissues. Three pathologists blinded to histology evaluated the sensitivity and specificity of optical coherence microscopy images to differentiate normal from neoplastic renal tissues. Results Optical coherence tomography and optical coherence microscopy images of normal kidney revealed architectural features, including glomeruli, convoluted tubules, collecting tubules and loops of Henle. Each method of imaging renal tumors clearly demonstrated morphological changes and decreased imaging depth. Optical coherence tomography and microscopy features matched well with the corresponding histology. Three observers achieved 88%, 100% and 100% sensitivity, and 100%, 88% and 100% specificity, respectively, when evaluating normal vs neoplastic specimens using optical coherence microscopy images with substantial interobserver agreement (κ = 0.82, p <0.01). Conclusions Integrated optical coherence tomography and optical coherence microscopy imaging provides coregistered, multiscale images of renal pathology in real time without exogenous contrast medium or histological processing. High sensitivity and specificity were achieved using optical coherence microscopy to differentiate normal from neoplastic renal tissues, suggesting possible applications for guiding renal mass biopsy or evaluating surgical margins.National Institutes of Health (U.S.) (NIH Grants R01-CA75289-14)National Institutes of Health (U.S.) (NIH R01-HL095717-02)United States. Air Force Office of Scientific Research (FA9550-10-1-0063)United States. Air Force Office of Scientific Research (FA9550-10-1-0551

A self-determination perspective of strengths use at work: Examining its determinant and performance implications

We investigate the role of strengths use in the workplace by drawing on self-determination theory (SDT) to propose that strengths use at work can yield performance benefits in terms of task performance and discretionary helping, and that the social context, in the form of leader autonomy support, can promote employees’ strengths use. Further, consistent with an interactional psychology perspective, we contend that the relationship between autonomy support and strengths use will be stronger among individuals with strong independent self-construal. We tested the model using matched data from 194 employees and their supervisors and found evidence for the relevance of strengths use at work, even after accounting for the role of intrinsic motivation. In addition to providing practical implications on developing employee strengths use and how to do so, this study advances theory and research on workplace strength use, SDT, and positive organizational behavior

Analysis and prediction of cancerlectins using evolutionary and domain information

<p>Abstract</p> <p>Background</p> <p>Predicting the function of a protein is one of the major challenges in the post-genomic era where a large number of protein sequences of unknown function are accumulating rapidly. Lectins are the proteins that specifically recognize and bind to carbohydrate moieties present on either proteins or lipids. Cancerlectins are those lectins that play various important roles in tumor cell differentiation and metastasis. Although the two types of proteins are linked, still there is no computational method available that can distinguish cancerlectins from the large pool of non-cancerlectins. Hence, it is imperative to develop a method that can distinguish between cancer and non-cancerlectins.</p> <p>Results</p> <p>All the models developed in this study are based on a non-redundant dataset containing 178 cancerlectins and 226 non-cancerlectins in which no two sequences have more than 50% sequence similarity. We have applied the similarity search based technique, i.e. BLAST, and achieved a maximum accuracy of 43.25%. The amino acids compositional analysis have shown that certain residues (e.g. Leucine, Proline) were preferred in cancerlectins whereas some other (e.g. Asparatic acid, Asparagine) were preferred in non-cancerlectins. It has been found that the PROSITE domain "Crystalline beta gamma" was abundant in cancerlectins whereas domains like "SUEL-type lectin domain" were found mainly in non-cancerlectins. An SVM-based model has been developed to differentiate between the cancer and non-cancerlectins which achieved a maximum Matthew's correlation coefficient (MCC) value of 0.32 with an accuracy of 64.84%, using amino acid compositions. We have developed a model based on dipeptide compositions which achieved an MCC value of 0.30 with an accuracy of 64.84%. Thereafter, we have developed models based on split compositions (2 and 4 parts) and achieved an MCC value of 0.31, 0.32 with accuracies of 65.10% and 66.09%, respectively. An SVM model based on Position Specific Scoring Matrix (PSSM), generated by PSI-BLAST, was developed and achieved an MCC value of 0.36 with an accuracy of 68.34%. Finally, we have integrated the PROSITE domain information with PSSM and developed an SVM model that has achieved an MCC value of 0.38 with 69.09% accuracy.</p> <p>Conclusion</p> <p>BLAST has been found inefficient to distinguish between cancer and non-cancerlectins. We analyzed the protein sequences of cancer and non-cancerlectins and identified interesting patterns. We have been able to identify PROSITE domains that are preferred in cancer and non-cancerlectins and thus provided interesting insights into the two types of proteins. The method developed in this study will be useful for researchers studying cancerlectins, lectins and cancer biology. The web-server based on the above study, is available at <url>http://www.imtech.res.in/raghava/cancer_pred/</url></p

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049