Biomarkers of chemotherapy-induced cardiotoxicity: toward precision prevention using extracellular vesicles

Detrimental side effects of drugs like doxorubicin, which can cause cardiotoxicity, pose barriers for preventing cancer progression, or treating cancer early through molecular interception. Extracellular vesicles (EVs) are valued for their potential as biomarkers of human health, chemical and molecular carcinogenesis, and therapeutics to treat disease at the cellular level. EVs are released both during normal growth and in response to toxicity and cellular death, playing key roles in cellular communication. Consequently, EVs may hold promise as precision biomarkers and therapeutics to prevent or offset damaging off-target effects of chemotherapeutics. EVs have promise as biomarkers of impending cardiotoxicity induced by chemotherapies and as cardioprotective therapeutic agents. However, EVs can also mediate cardiotoxic cues, depending on the identity and past events of their parent cells. Understanding how EVs mediate signaling is critical toward implementing EVs as therapeutic agents to mitigate cardiotoxic effects of chemotherapies. For example, it remains unclear how mixtures of EV populations from cells exposed to toxins or undergoing different stages of cell death contribute to signaling across cardiac tissues. Here, we present our perspective on the outlook of EVs as future clinical tools to mitigate chemotherapy-induced cardiotoxicity, both as biomarkers of impending cardiotoxicity and as cardioprotective agents. Also, we discuss how heterogeneous mixtures of EVs and transient exposures to toxicants may add complexity to predicting outcomes of exogenously applied EVs. Elucidating how EV cargo and signaling properties change during dynamic cellular events may aid precision prevention of cardiotoxicity in anticancer treatments and development of safer chemotherapeutics

Multicenter evaluation of the clinical utility of laparoscopy-assisted ERCP in patients with Roux-en-Y gastric bypass

Background and Aims The obesity epidemic has led to increased use of Roux-en-Y gastric bypass (RYGB). These patients have an increased incidence of pancreaticobiliary diseases yet standard ERCP is not possible due to surgically altered gastroduodenal anatomy. Laparoscopic-ERCP (LA-ERCP) has been proposed as an option but supporting data are derived from single center small case-series. Therefore, we conducted a large multicenter study to evaluate the feasibility, safety, and outcomes of LA-ERCP. Methods This is retrospective cohort study of adult patients with RYGB who underwent LA-ERCP in 34 centers. Data on demographics, indications, procedure success, and adverse events were collected. Procedure success was defined when all of the following were achieved: reaching the papilla, cannulating the desired duct and providing endoscopic therapy as clinically indicated. Results A total of 579 patients (median age 51, 84% women) were included. Indication for LA-ERCP was biliary in 89%, pancreatic in 8%, and both in 3%. Procedure success was achieved in 98%. Median total procedure time was 152 minutes (IQR 109-210) with median ERCP time 40 minutes (IQR 28-56). Median hospital stay was 2 days (IQR 1-3). Adverse events were 18% (laparoscopy-related 10%, ERCP-related 7%, both 1%) with the clear majority (92%) classified as mild/moderate whereas 8% were severe and 1 death occurred. Conclusion Our large multicenter study indicates that LA-ERCP in patients with RYGB is feasible with a high procedure success rate comparable with that of standard ERCP in patients with normal anatomy. ERCP-related adverse events rate is comparable with conventional ERCP, but the overall adverse event rate was higher due to the added laparoscopy-related events

Percutaneous transhepatic vs. endoscopic retrograde biliary drainage for suspected malignant hilar obstruction: study protocol for a randomized controlled trial

Abstract Background The optimal approach to the drainage of malignant obstruction at the liver hilum remains uncertain. We aim to compare percutaneous transhepatic biliary drainage (PTBD) to endoscopic retrograde cholangiography (ERC) as the first intervention in patients with cholestasis due to suspected malignant hilar obstruction (MHO). Methods The INTERCPT trial is a multi-center, comparative effectiveness, randomized, superiority trial of PTBD vs. ERC for decompression of suspected MHO. One hundred and eighty-four eligible patients across medical centers in the United States, who provide informed consent, will be randomly assigned in 1:1 fashion via a web-based electronic randomization system to either ERC or PTBD as the initial drainage and, if indicated, diagnostic procedure. All subsequent clinical interventions, including crossover to the alternative procedure, will be dictated by treating physicians per usual clinical care. Enrolled subjects will be assessed for successful biliary drainage (primary outcome measure), adequate tissue diagnosis, adverse events, the need for additional procedures, hospitalizations, and oncological outcomes over a 6-month follow-up period. Subjects, treating clinicians and outcome assessors will not be blinded. Discussion The INTERCPT trial is designed to determine whether PTBD or ERC is the better initial approach when managing a patient with suspected MHO, a common clinical dilemma that has never been investigated in a randomized trial. Trial registration ClinicalTrials.gov, Identifier: NCT03172832 . Registered on 1 June 2017.https://deepblue.lib.umich.edu/bitstream/2027.42/142379/1/13063_2018_Article_2473.pd

Sewer System Alternatives Evaluation for Potential Creswell Area Expansion in Harford County

Final project for ENCE422: Project Cost Accounting and Economics (Fall 2018). University of Maryland, College Park.This report summarizes the findings of the ENCE422 Fall 2018 class term project. Students were tasked with evaluating sewer system alternatives for the Creswell area expansion in Harford County. Student groups were to consider environmental impacts, community/social impacts, and perform financial analysis for the alternatives they chose to evaluate. This report extracts information from 14 separate team presentations and synthesizes it around the following structure; 1. Systems that Utilize Septic Tanks a. Traditional Septic System b. Orenco Effluent System c. Small Diameter Gravity Sewer System 2. System that Do Not Utilize Septic Tanks a. Traditional Gravity System b. Vacuum System c. Grinder Pump SystemHarford Count

Bali İklim Görüşmelerinde Neden Gerçek Bir İlerleme Sağlanamadı?

Bu tip toplantılara genelde hâkim olan tüm o şamata içinde, Endonezya’nın Bali adasındaki iklim konferansına katılan delegeler evlerine zafer kazandıklarını ilan ederek döndüler. ABD delegasyonunun yoğun engelleme çabalarına karşın, müzakereciler sera gazı emisyonlarının indirimi için müzakerelere devam etmek üzere yumuşak bir uzlaşıya vardırlar ve metni imzalaması için ABD’yi son dakikada kandırmayı ve sıkıştırmayı başardılar

Monsanto: Una historia en entredicho

Monsanto is the main enterprise in transgenic research in staple foods. lts history is full of non ethicintentions since 1 920. PCB's (polichlorinated bipheniles) are one of the first Monsanto's chemical compounds with hughe problems of bioconcentration. The content of dioxines in several of its chemical products is very important, not only among users, also in Monsanto's workers. This problem was analyzed after the exposition to Orange Agent in Vietnam's vets. Transgenic soy is not sent to the market to solution world's lamine, in stead of forcing farmers to use the herbicide (Round up) associated with transgenic soy. Similar are the exeriencies with rBGH (recombinant bovine growth hormone), used to enhance milk production in cows, with many health problems to the livestock. Due to the growing concern of public opinion against transgenic industry, monsanto has launched a "Greenwash" policy , treating to associate "green" and "ecological" projects with one of the 5 more contaminating industries of USA. This work is copied from "The Ecologist" and represents the concern of NATURA MEDICATRIX with liberty of expression

Redesigning life? The worldwide challenge to genetic engineering /

Includes bibliographical references and index

Cell-free DNA as a potential biomarker of differentiation and toxicity in cardiac organoids

Cell-free DNA (cfDNA) present in the bloodstream or other bodily fluids holds potential as a noninvasive diagnostic for early disease detection. However, it remains unclear what cfDNA markers might be produced in response to specific tissue-level events. Organoid systems present a tractable and efficient method for screening cfDNA markers. However, research investigating the release of cfDNA from organoids is limited. Here, we present a scalable method for high-throughput screening of cfDNA from cardiac organoids. We demonstrate that cfDNA is recoverable from cardiac organoids, and that cfDNA release is the highest early in differentiation. Intriguingly, we observed that the fraction of cell-free mitochondrial DNA appeared to decrease as the organoids developed, suggesting a possible signature of cardiac organoid maturation, or other cardiac growth-related tissue-level events. We also observe alterations in the prevalence of specific genomic regions in cardiac organoid-derived cfDNA at different timepoints during growth. In addition, we identify cfDNA markers that were increased upon addition of cardiotoxic drugs, prior to the onset of tissue demise. Together, these results indicate that cardiac organoids may be a useful system towards the identification of candidate predictive cfDNA markers of cardiac tissue development and demise