Assessing the Impact of Circulating Tumor DNA (ctDNA) in Patients With Colorectal Cancer: Separating Fact From Fiction

Significant advances and increased awareness have been in made in the field of non-invasive liquid biopsies for cancer, spanning several malignancies from gastrointestinal, pulmonary, and other etiologies. Broadly, the genetic source material for liquid biopsies includes circulating tumor cells, cell-free circulating tumor DNA (ctDNA), or cell-free circulating tumor microRNA (mRNA). In this review, we specifically focus on ctDNA and its current role in colorectal cancer. While there are several commercially available assays that detect ctDNA, the utility of these products is still variable and therefore the clinical applications of ctDNA in the management of patients with cancer has yet to be determined. This is reflected by the recent joint review set forth by the American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP), clarifying and somewhat tempering the present role of ctDNA in patients with cancer. This review provides additional detail regarding ctDNA in the limited setting of colorectal cancer. The increasing importance and promise of ctDNA remains an area of active research, and further prospective studies may enhance the clinical utility of ctDNA in the future

Синтез та характеристика екологічно чистої та схильної до біологічного розкладання плівки ізоляту соєвого білка

У дослідженні біосумісна та схильна до біологічного розкладання плівка ізоляту соєвого білка (SPI) була розроблена шляхом включення полярних компонентів за допомогою техніки лиття. Вплив додаткових компонентів (гліцерин, сорбітол та поліетиленгліколь) з SPI аналізували за допомогою скануючої електронної мікроскопії (SEM), інфрачервоної спектроскопії з перетворенням Фур'є (FTIR) та рентгенівської дифракції (XRD). Результат підтвердив, що включення полярних компонентів з ізолятом соєвого білка демонструє сильну міжмолекулярну взаємодію. Це найпростіший метод розробки біосумісних плівок, які мають широке застосування в біомедицині, біотехнології, безпеці харчових продуктів та промисловості їх пакування.In the current study, biocompatible and biodegradable soy protein isolate (SPI) based film was developed by incorporating polar components using casting technique. The effects of additive components (glycerol, sorbitol and polyethylene glycol) with SPI were analyzed by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD). The result confirmed that the incorporation of polar components with soy protein isolate exhibits strong intermolecular interaction. This is the easiest method to develop biocompatible films that have wide applications in biomedical, biotechnology, food safety and food packaging industries

Spatial Metagenomic Analysis in Understanding the Microbial Diversity of Thar Desert

The arid and semi-arid regions of Rajasthan are one of the most extreme biomes of India, possessing diverse microbial communities that exhibit immense biotechnological potential for industries. Herein, we sampled study sites from arid and semi-arid regions of Thar Desert, Rajasthan, India and subjected them to chemical, physical and metagenomics analysis. The microbial diversity was studied using V3–V4 amplicon sequencing of 16S rRNA gene by Illumina MiSeq. Our metagenomic analyses revealed that the sampled sites consist mainly of Proteobacteria (19–31%) followed by unclassified bacteria (5–21%), Actinobacteria (3–25%), Planctomycetes (5–13%), Chloroflexi (2–14%), Bacteroidetes (3–12%), Firmicutes (3–7%), Acidobacteria (1–4%) and Patescibacteria (1–4%). We have found Proteobacteria in abundance which is associated with a range of activities involved in biogeochemical cycles such as carbon, nitrogen, and sulphur. Our study is perhaps the first of its kind to explore soil bacteria from arid and semi-arid regions of Rajasthan, India. We believe that the new microbial candidates found can be further explored for various industrial and biotechnological applications

Human intravital microscopy in the study of sarcomas: an early trial of feasibility

Sarcomas comprise a vast and heterogenous group of rare tumors. Because of their diversity, it is challenging to study sarcomas as a whole with regard to their biological and molecular characteristics. This diverse set of tumors may also possess differences related to their tumor-associated vasculature, which in turn may impact the ability to deliver systemic therapies (e.g., chemotherapy, targeted therapies, and immunotherapy). Consequently, response to systemic treatment may also be variable as these depend on the ability of the therapy to reach the tumor target via the tumor-associated vasculature. There is a paucity of data regarding sarcoma-related tumor vessels, likely in part to the rarity and heterogeneity of this cancer as well as the previously limited ability to image tumor-associated vessels in real time. Our group has previously utilized confocal fluorescent imaging technology to observe and characterize tumor-associated vessels in real time during surgical resection of tumors, including cutaneous melanoma and carcinomatosis implants derived from gastrointestinal, gynecological, or primary peritoneal (e.g., mesothelioma) tumors. Our prior studies have demonstrated the feasibility of real-time, human intravital microscopy in the study of these tumor types, leading to early but important new data regarding tumor vessel characteristics and their potential implications on drug delivery and efficacy. In this brief report, we present our latest descriptive findings in a cohort of patients with sarcoma who underwent surgical resection and real-time, intravital microscopy of their tumors. Overall, intravital imaging was feasible during the surgical resection of large sarcomas.Clinical trial registrationsClinicalTrials.gov, identifier NCT03517852; ClinicalTrials.gov, identifier NCT03823144

Health Impacts of Catastrophic Climate Change: Expert Workshop. Avoid Dangerous Climate Change (AVOID)

Climate change is likely to have serious and significant impacts on human population health. The mechanisms by which climate change may affect health are becoming better understood. Current quantitative methods of estimating future health impacts rely on disease-specific models that primarily describe relationships between mean values of weather variables and health outcomes and do not address the impacts of extreme events or weather disasters. Extreme events have the potential to disrupt community function, which is of concern for decision-makers. Estimating the magnitude and extent of impacts from low probability high impact events is challenging because there is often no analogue that can provide relevant evidence and that take into account the complexity of factors determining future vulnerability and health impacts (the social determinants of health)

Impaired Function of Antibodies to Pneumococcal Surface Protein A but not to Capsular Polysaccharide in Mexican American Adults with Type 2 Diabetes Mellitus

The goal of the study was to determine baseline protective titers of antibodies to Streptococcus pneumoniae surface protein A (PspA) and capsular polysaccharide in individuals with and individuals without type 2 diabetes mellitus. A total of 561 individuals (131 individuals with diabetes and 491 without) were screened for antibodies to PspA using a standard enzyme-linked immunosorbent assay (ELISA). A subset of participants with antibodies to PspA were retested using a WHO ELISA to determine titers of antibodies to capsular polysaccharide (CPS) (serotypes 4, 6B, 9V, 14, 18C, 19A, 19F, and 23F). Functional activity of antibodies was measured by assessing their ability to enhance complement (C3) deposition on pneumococci and promote killing of opsonized pneumococci. Titers of antibodies to protein antigens (PspA) were significantly lower in individuals with diabetes than controls without diabetes (P = 0.01), and antibodies showed a significantly reduced complement deposition ability (P = 0.02). Both antibody titers and complement deposition were negatively associated with hyperglycemia. Conversely, titers of antibodies to capsular polysaccharides were either comparable between the two groups or were significantly higher in individuals with diabetes, as was observed for CPS 14 (P = 0.05). The plasma specimens from individuals with diabetes also demonstrated a higher opsonophagocytic index against CPS serotype 14. Although we demonstrate comparable protective titers of antibodies to CPS in individuals with and individuals without diabetes, those with diabetes had lower PspA titers and poor opsonic activity strongly associated with hyperglycemia. These results suggest a link between diabetes and impairment of antibody response.CCTS 1U54RR023417-01National Center on Minority Health and Health Disparities (NCMHD) MD000170 P20Centers for Clinical and Translational Science from the National Center for Research Resources (NCRR)Cellular and Molecular Biolog

Pla funcional del programa d’intercanvi de xeringues a les farmàcies comunitàries

Programa d'intercanvi de xeringues; Farmàcies comunitàries; Guia del farmacèuticPrograma de intercambio de jeringas; Farmacias comunitarias; Guía del farmacéuticoSyringe exchange program; Community pharmacies; Guide to the pharmacistAquest document pretén ser una eina de suport per a farmacèutics i farmacèutiques comunitàries en la implementació i el desenvolupament del PIX. Després d’una primera part introductòria sobre els programes de reducció de danys i la seva evolució, s’aborda amb detall el programa d’intercanvi de xeringues a les farmàcies comunitàries, per tal que el professional que el vulgui posar en marxa a la seva farmàcia disposi dels coneixements i les eines necessàries per poder-ho fer. La guia es complementa amb informacions addicionals sobre temes vinculats al programa, com ara el consum de drogues, la xarxa d’atenció a les drogodependències i orientació sobre educació sanitària, entre altres.This document aims to be a support tool for community pharmacists and pharmacists in the implementation and development of the PIX. After a first introductory part about the harm reduction programs and their evolution, the syringe exchange program is discussed in detail in community pharmacies, so that the professional who wishes to start their work The pharmacy has the necessary knowledge and tools to do it. The guide is complemented by additional information on topics related to the program, such as drug use, the drug care network, and guidance on health education, among othersEste documento pretende ser una herramienta de apoyo para farmacéuticos y farmacéuticas comunitarias en la implementación y el desarrollo del PIX. Tras una primera parte introductoria sobre los programas de reducción de daños y su evolución, se aborda con detalle el programa de intercambio de jeringuillas en las farmacias comunitarias, para que el profesional que lo quiera poner en marcha a su farmacia disponga de los conocimientos y las herramientas necesarias para poder hacerlo. La guía se complementa con informaciones adicionales sobre temas vinculados al programa, tales como el consumo de drogas, la red de atención a las drogodependencias y orientación sobre educación sanitaria, entre otro

Evaluation of cell-free DNA approaches for multi-cancer early detection

In the Circulating Cell-free Genome Atlas (NCT02889978) substudy 1, we evaluate several approaches for a circulating cell-free DNA (cfDNA)-based multi-cancer early detection (MCED) test by defining clinical limit of detection (LOD) based on circulating tumor allele fraction (cTAF), enabling performance comparisons. Among 10 machine-learning classifiers trained on the same samples and independently validated, when evaluated at 98% specificity, those using whole-genome (WG) methylation, single nucleotide variants with paired white blood cell background removal, and combined scores from classifiers evaluated in this study show the highest cancer signal detection sensitivities. Compared with clinical stage and tumor type, cTAF is a more significant predictor of classifier performance and may more closely reflect tumor biology. Clinical LODs mirror relative sensitivities for all approaches. The WG methylation feature best predicts cancer signal origin. WG methylation is the most promising technology for MCED and informs development of a targeted methylation MCED test

Real-Time Cytotoxicity Assay for Rapid and Sensitive Detection of Ricin from Complex Matrices

BACKGROUND: In the context of a potential bioterrorist attack sensitive and fast detection of functionally active toxins such as ricin from complex matrices is necessary to be able to start timely countermeasures. One of the functional detection methods currently available for ricin is the endpoint cytotoxicity assay, which suffers from a number of technical deficits. METHODOLOGY/FINDINGS: This work describes a novel online cytotoxicity assay for the detection of active ricin and Ricinus communis agglutinin, that is based on a real-time cell electronic sensing system and impedance measurement. Characteristic growth parameters of Vero cells were monitored online and used as standardized viability control. Upon incubation with toxin the cell status and the cytotoxic effect were visualized using a characteristic cell index-time profile. For ricin, tested in concentrations of 0.06 ng/mL or above, a concentration-dependent decrease of cell index correlating with cytotoxicity was recorded between 3.5 h and 60 h. For ricin, sensitive detection was determined after 24 h, with an IC50 of 0.4 ng/mL (for agglutinin, an IC50 of 30 ng/mL was observed). Using functionally blocking antibodies, the specificity for ricin and agglutinin was shown. For detection from complex matrices, ricin was spiked into several food matrices, and an IC50 ranging from 5.6 to 200 ng/mL was observed. Additionally, the assay proved to be useful in detecting active ricin in environmental sample materials, as shown for organic fertilizer containing R. communis material. CONCLUSIONS/SIGNIFICANCE: The cell-electrode impedance measurement provides a sensitive online detection method for biologically active cytotoxins such as ricin. As the cell status is monitored online, the assay can be standardized more efficiently than previous approaches based on endpoint measurement. More importantly, the real-time cytotoxicity assay provides a fast and easy tool to detect active ricin in complex sample matrices