Development of label-free detection systems targeting food-borne pathogens

Food-borne pathogens and food safety-related outbreaks have come to the forefront over recent years. Estimates on the annual cost of sicknesses, hospitalizations, and deaths run into the billions of dollars. There is a large body of research on the subject of detection of food-borne pathogens, however, the widely accepted current systems are limited by high reagent costs, lengthy time to completion, and expensive equipment. This work has been developed with the goal of focusing on minimizing the time and reagent cost of two of the most common types of rapid, food-borne pathogen detection systems, i.e. immunoassays and real-time polymerase chain reaction assays. The first aim was to develop the proof-of-concept methodology for a label-free immunoassay technique utilizing photonic crystal biosensors targeting bacteria, specifically E. coli O157:H7. In this project, it is shown that detergent-lysing of the cells and extraction of their membrane antigens allows for the detection of down to 1E7 CFU/mL. Optimization of the blocking scheme takes the assay one step further and allows for specific detection of E. coli O157:H7 over E. coli K12. The second aim was to develop a label-free method for determining changes in DNA concentration as it relates to food-borne pathogen-targeted polymerase chain reaction assays. For this goal, impedance spectroscopy studies were carried out to characterize the system???s capability in determining changes in concentration of purified DNA in DI water. To adequately measure the change in DNA concentration in a PCR solution, it was necessary to go through a purification and precipitation step to minimize the effects of primers, PCR reagents, and especially excess salts. It was shown that the purification and precipitation of the fully amplified PCR reaction showed a similar trend to the pure DNA in DI water characterization tests. In developing the two versions of label-free detection systems, this work has brought cheaper, faster, smaller biosensors one step closer to reality

Hormonal crises following receptor radionuclide therapy with the radiolabeled somatostatin analogue [177Lu-DOTA0,Tyr3]octreotate

textabstractIntroduction: Receptor radionuclide therapy is a promising treatment modality for patients with neuroendocrine tumors for whom alternative treatments are limited. The aim of this study was to investigate the incidence of hormonal crises after therapy with the radiolabeled somatostatin analogue [177Lu-DOTA0,Tyr3]octreotate (177Lu-octreotate). Materials and methods: All177Lu- octreotate treatments between January 2000 and January 2007 were investigated. Four hundred seventy-six patients with gastroenteropancreatic neuroendocrine tumors and three patients with metastatic pheochromocytoma were included for analysis. Results: Four hundred seventy-nine patients received a total of 1,693 administrations of177Lu-octreotate. Six of 479 patients (1%) developed severe symptoms because of massive release of bioactive substances after the first cycle of177Lu-octreotate. One patient had a metastatic hormone-producing small intestinal carcinoid; two patients had metastatic, hormone-producing bronchial carcinoids; two patients had vasoactive intestinal polypeptide-producing pancreatic endocrine tumors (VIPomas); and one patient had a metastatic pheochromocytoma. With adequate treatment, all patients eventually recovered. Conclusion: Hormonal crises after177Lu- octreotate therapy occur in 1% of patients. Generally,177Lu- octreotate therapy is well tolerated

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