Multimodal epigenetic sequencing analysis (MESA) of cell-free DNA for non-invasive colorectal cancer detection.

BACKGROUND: Detecting human cancers through cell-free DNA (cfDNA) in blood is a sensitive and non-invasive option. However, capturing multiple forms of epigenetic information remains a technical and financial challenge. METHODS: To address this, we developed multimodal epigenetic sequencing analysis (MESA), a flexible and sensitive approach to capturing and integrating a diverse range of epigenetic features in cfDNA using a single experimental assay, i.e., non-disruptive bisulfite-free methylation sequencing, such as Enzymatic Methyl-seq. MESA enables simultaneous inference of four epigenetic modalities: cfDNA methylation, nucleosome occupancy, nucleosome fuzziness, and windowed protection score for regions surrounding gene promoters and polyadenylation sites. RESULTS: When applied to 690 cfDNA samples from 3 colorectal cancer clinical cohorts, MESA's novel modalities, which include nucleosome fuzziness, and genomic features, including polyadenylation sites, improve cancer detection beyond the traditional epigenetic markers of promoter DNA methylation. CONCLUSIONS: Together, MESA stands as a major advancement in the field by utilizing comprehensive and complementary epigenetic profiles of cfDNA for effective non-invasive cancer detection.

Common postoperative complications after general anesthesia in oral and maxillofacial surgery.

AIM AND OBJECTIVES: Anesthesia is Greek word meaning loss of sensation, and involves painful invasive procedure to be performed with little distress and no pain to the patient. Postoperative anesthetic complications are very common and duration of surgery is frequently cited as major risk factor for postoperative complications. The recognition and treatment of these complications are important when providing good quality care. The purpose of this study was to evaluate mild, moderate, and severe postoperative complications in patients undergoing maxillofacial surgery under general anesthesia and also determine the safety of general anesthesia in healthy and patients with comorbidities. SUBJECTS AND METHODS: This prospective study was conducted in the oral and maxillofacial surgery department. Two hundred and twenty patients who were operated under general anesthesia were taken in study. All relevant past medical and dental records were noted and were supported by preformulated questionnaire and was filled preoperatively and after surgery to 12 weeks. RESULTS: Mild-to-moderate and severe complications were noted. Females showed more complications than males. Most common complications were sore throat, dysphagia, nausea, vomiting, pain, swelling in normal patients, and in patients with comorbidities delayed wound healing, hypertension, and infection were also seen. CONCLUSION: The use of General Anesthesia is considered safe but it has few risks associated with it and past medical conditions should be evaluated preoperatively.

Impact of a standardized reporting format on the quality of MRI reports for rectal cancer staging.

BACKGROUND AND AIMS: Besides providing a surgical roadmap, rectal MRI plays a major role in treatment planning. We recently started using a structured template for reporting rectal cancer via MRI. We study the impact of using this template at our hospital in terms of number of essential imaging parameters described in the reports as compared to the pre-template free-text reports. METHODS: A structured rectal MRI reporting template was created in consensus with members of the colorectal tumour board and was introduced in the department, which included 14 essential parameters to be mentioned in the reports. We conducted a retrospective analysis of rectal MRI reports of 100 cases with histologically proven rectal cancer, comprising 50 consecutive free-text reports before the template was introduced and 50 consecutive structured reports after its introduction, checking for the presence or absence of inclusion of the 14 parameters. An anonymous online feedback survey was conducted as well after the introduction of the template for the members of the colorectal tumour board. RESULTS: Overall, the total number of parameters reported increased from a median value of 10 (range 6-13) to 14 (range 12-14). The common unreported parameters prior to template introduction included T staging, presence or absence of restricted diffusion, anterior peritoneal reflection (APR) involvement, and presence or absence of extramural vascular invasion; these were reported in 16%, 22%, 30% and 50% respectively. These improved to 98-100% reporting after template introduction. Maximum improvement was in T staging (16% to 98%) (P < 0.0001), restricted diffusion on DWI (from 22% to 100%) (P < 0.0001) and APR involvement (from 30% to 100%) (P < 0.0001). The most common unreported parameter after template introduction was the "tumoral T2 signal intensity" (unreported in 4% cases). The results of the survey were as follows: 100% felt a decreased need to talk to the radiologist to clarify the report, 81.8% felt an improvement in the quality of reporting as compared to free style reports, and 91% felt that the new template is easier to interpret. CONCLUSION: The introduction of a structured template for rectal cancer significantly improved the quality of rectal MRI reports, along with the satisfaction of referring providers.

Correction to: The Continuing Evolution of Molecular Functional Imaging in Clinical Oncology: The Road to Precision Medicine and Radiogenomics (Part II).

An Online First version of this article was made available online at http://link.springer.com/journal/40291/onlineFirst/page/1 on 01 Nov 2018. An error was subsequently identified in the article, and the following correction should be noted.

The Continuing Evolution of Molecular Functional Imaging in Clinical Oncology: The Road to Precision Medicine and Radiogenomics (Part I).

The present era of precision medicine sees 'cancer' as a consequence of molecular derangements occurring at the commencement of the disease process, with morphologic changes happening much later in the process of tumorigenesis. Conventional imaging techniques, such as computed tomography (CT), ultrasound, and magnetic resonance imaging (MRI), play an integral role in the detection of disease at a macroscopic level. However, molecular functional imaging (MFI) techniques entail the visualisation and quantification of biochemical and physiological processes occurring during tumorigenesis, and thus has the potential to play a key role in heralding the transition from the concept of 'one size fits all' to 'precision medicine'. Integration of MFI with other fields of tumour biology such as genomics has spawned a novel concept called 'radiogenomics', which could serve as an indispensable tool in translational cancer research. With recent advances in medical image processing, such as texture analysis, deep learning, and artificial intelligence (AI), the future seems promising; however, their clinical utility remains unproven at present. Despite the emergence of novel imaging biomarkers, a majority of these require validation before clinical translation is possible. In this two-part review, we discuss the systematic collaboration across structural, anatomical, and molecular imaging techniques that constitute MFI. Part I reviews positron emission tomography, radiogenomics, AI, and optical imaging, while part II reviews MRI, CT and ultrasound, their current status, and recent advances in the field of precision oncology.

The Continuing Evolution of Molecular Functional Imaging in Clinical Oncology: The Road to Precision Medicine and Radiogenomics (Part II).

The present era of precision medicine sees "cancer" as a consequence of molecular derangements occurring at the commencement of the disease process, with morphological changes happening much later in the process of tumourigenesis. Conventional imaging techniques, such as computed tomography (CT), ultrasound (US) and magnetic resonance imaging (MRI) play an integral role in the detection of disease at the macroscopic level. However, molecular functional imaging (MFI) techniques entail the visualisation and quantification of biochemical and physiological processes occurring during tumourigenesis. MFI has the potential to play a key role in heralding the transition from the concept of "one-size-fits-all" treatment to "precision medicine". Integration of MFI with other fields of tumour biology such as genomics has spawned a novel concept called "radiogenomics", which could serve as an indispensable tool in translational cancer research. With recent advances in medical image processing, such as texture analysis, deep learning and artificial intelligence, the future seems promising; however, their clinical utility remains unproven at present. Despite the emergence of novel imaging biomarkers, the majority of these require validation before clinical translation is possible. In this two part review, we discuss the systematic collaboration across structural, anatomical and molecular imaging techniques that constitute MFI. Part I reviews positron emission tomography, radiogenomics, AI, and optical imaging, while part II reviews MRI, CT and ultrasound, their current status, and recent advances in the field of precision oncology.

Design, Synthesis and Biological Evaluation of 7-arylbenzo[c]acridine-5,6- diones as Potential Anti-Leishmanial and anti-trypanosomal Agents.

BACKGROUND: Leishmaniasis is endemic in 98 countries and is closely associated with poverty. On the basis of current evidence, it may be safely suggested that over time Leishmania spp. have evolved coexistence in different macrophage types and developed adaptations in order to ensure their intracellular survival. Considering new drugs, the need of the hour the present study deals with the synthesis of novel compounds of biological importance based on naturally occurring scaffolds. OBJECTIVE: Synthesis, anti-leishmanial and anti-trypanosomal activities of a series of thirty three (eighteen newly synthesized and fifteen previously reported) 7-arylbenzo[c]acridine-5,6-diones. METHOD: A series of thirty-three 7-arylbenzo[c]acridine-5,6-diones was designed and synthesized. The anti-leishmanial and anti-trypanosomal activities of the newly synthesized compounds were done. RESULTS: Seven compounds (14, 17, 19, 26, 27, 38 and 39) were found to exhibit excellent antiparasitic activities. Compound 14 was identified as the most potent compound against L. donovani promastigotes while compound 27 showed most significant inhibition activity against amastigotes. Compounds 14 and 27 showed remarkable inhibitory activity with IC50 values of 0.38 and 0.53 µM, respectively, when tested in human macrophage cell line (THP) infected with L. donovani amastigotes. Against trypanomastigotes, six compounds (15, 17, 19, 25, 26 and 43) demonstrated remarkable inhibition. CONCLUSION: Compound 19 was found to be the best anti-trypanosomal agent and showed 300-fold superior inhibitory activity to that of the standard drug DFMO. Significant anti-leishmanial and anti-trypanosomal activities combined with the non-cytotoxic profile presents 7-arylbenzo[c]acridine- 5,6-diones as new candidates with therapeutic potential in the treatment of parasitic diseases.

Berberine and its derivatives: a patent review (2009 - 2012).

INTRODUCTION: Berberine, a protoberberine alkaloid, and its derivatives exhibit a wide spectrum of pharmacological activities. It has been used in traditional Chinese medicine and Ayurvedic medicine and current research evidences support its use for various therapeutic areas. AREAS COVERED: This review covers the patents on therapeutic activities of berberine and its derivatives in the years between 2009 and 2012. An extensive search was done to collect the patent information using European Patent Office database and SciFinder. The therapeutic areas covered include cancer, inflammation, infectious diseases, cardiovascular, metabolic disorders, and miscellaneous areas such as polycystic ovary syndrome, allergic diseases, and so on. EXPERT OPINION: Berberine along with its derivatives or in combination with other pharmaceutically active compounds or in the form of formulations has applications in various therapeutic areas such as cancer, inflammation, diabetes, depression, hypertension, and various infectious areas. Berberine has demonstrated wide physiological functions and has great potential to give a multipotent drug if some inherent problems on poor bioavailability and solubility are taken care of. Additionally, polyherbal formulations with berberine-containing plants as major ingredients can be successfully developed.