Search

Current methods to recover circulating tumour cells (CTCs) from the peripheral blood circulation of carcinoma patients rely principally on the expression of epithelial markers such as EpCAM, physical characteristics, and the absence of hematopoietic biomarkers. However, this strategy favours recovery of a homogeneous cell population with primarily differentiated epithelial characteristics. It fails to fully include those subpopulations that do not fit predictions and in particular does not properly capture cells that have stem-like characteristics or have undergone epithelial-mesenchymal transition (EMT). Yet these are often the cells that are most likely to give rise to successful metastasis and contribute to disease progression. We favour an approach that anticipates cellular heterogeneity, includes cells that have poor expression of differentiated characteristics, and relies on the very functional properties that are involved in successful negotiation of the route that culminates in metastasis. We therefore use a ‘tuned ECM’ (tECM) approach in which a complex ECM substratum is designed to extract and recover heterogeneous CTCs from the blood of patients with the cancer of interest, allowing subsequent single-cell analysis of cell behaviours to inform on features that have been shown to predict disease progression and metastasis. In the work described here we first used model colorectal cancer (CRC) cell lines, including those made resistant to drugs used in CRC regimens, to establish the best composition of ECM and full procedure to maximally capture cells for functional evaluation. For CRC we identified a defined mixture of collagen I and human plasma fibronectin as optimal for cell capture, providing a total recovery equivalent to complex ECM derived from tumor sources. In addition, this mixture accentuated the recovery of CRC cells made resistant to SN-38, the active metabolite of irinotecan. We then applied this approach to the recovery of CTCs from the blood from patients with stage IV CRC, using density centrifugation for prefractionation of nucleated blood cells followed by incubation on the tECM substratum. The captured cells could be immunostained in situ for both cytoplasmic and cell-surface markers and showed suitability for future assessment of cell behaviours in unfixed preparations. Optimisation of the capture-surface coating concentrations and subsequent fixation approach led to a 128-fold improvement in the CTC capture and identification from CRC patient blood. This optimised tECM approach offers promise for future inclusive recovery of heterogeneous CTC samples based on functional behaviours that relate to the metastastic process of the particular carcinoma, permitting further analyses including of chemokine pathways that are believed to be important in CRC metastasis. Citation Format: Deep Patel, Mala Bahl, Mario Valdes, Jonathan Blay. Utilization of optimized extracellular matrix substratum for inclusive capture of circulating tumor cells in stage IV colorectal cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PO-065.

Various technologies have been developed for safer and more comfortable road travel. Intelligent Transportation Systems (ITS) are being adopted for numerous purposes to solve traffic problems. In this paper, an in-vehicle system capable of avoiding or lessening the impact of collision is designed, developed, and validated. Analysis has also been done on an Indian road to check the reliability of the data obtained. The system detects the obstacles around the vehicle and issues warning to the driver. Study provides in-depth analysis and methodology in order to warn about safe distance, which will help in decision-making of driver to reduce the impact of collision. Impact Reduction Scheme also provides cause of accidents which may help in formulating an effective, verifiable, and justified insurance claim and redress system.

The WNT/β-catenin cellular network has been extensively studied in numerous diseases including inflammatory bowel disease (IBD). IBD is a condition that increases the risk of developing colorectal cancer. WIF-1 is an inhibitory protein that acts by blocking the interactions of WNT with its receptor complex, thus leading to downregulation of end products of this pathway. While WIF-1 has been characterized in several cancers, its relationship with IBD has yet to be elucidated. In this study, the expression of WIF-1 in patients with IBD was analyzed in order to provide insights into the pathophysiology and rationale for alternative therapies. Biopsies of both normal and inflamed colonic mucosa from patients with Crohn's disease or ulcerative colitis were histologically examined for the degree of morphologic changes, immune cell infiltration and presence of WIF-1 through immunohistochemistry. No differences were observed in WIF-1 expression linked to a particular condition, but WIF-1 stain was significantly enhanced in the crypts and lamina propria as inflammation increased in biopsies from patients with both, ulcerative colitis and Crohn's disease. These findings could give guidance to new therapeutic applications of the WNT/β-catenin system and WIF-1 in IBD.

In manufacturing sector, production time is an important factor in order to compete in market. This leads every management to decrease production time and increase quality of the product. In manufacturing industry in the production of product the main two kind of time consumption are Machining time and travel time also known as value added and non-value added time. Sometimes unnecessary or improper work cycle leads to delay in manufacturing. Hence, it is most important to identify that delay and minimize for positive benefit of company. As most of the industries bear losses due to nonproductive time in the manufacturing cycle and this paper give one of many solutions to increase the productive time. The main objective of this paper is to explain how the plant layout can with help of Motion study and Work Measurement to reduce lead-time and the manufacturing cycle time.

Background A number of barriers prevent community pharmacists (CPs) from impacting public health (PH) outcomes. Social media (SM) and mobile health apps (MH apps) may offer ways to help the public make positive health decisions. Objectives To evaluate CP perceptions of their role in PH and the use of SM and MH apps in this regard. Methods This was a mixed method study using a cross-sectional survey and follow-up interviews. The survey covered: CPs role in PH; CP use of SM; CP use of MH apps; non-identifiable demographic information. Following ethical approval and piloting, responses were collected on paper and online. The study population was CPs in Greater London, UK (n = 2931). A minimum sample size of 340 was calculated (95% confidence interval/5% margin of error). To achieve this, 596 surveys were distributed. Responses (n = 257) were analysed using descriptive statistics. Twenty-five respondents were willing to take part in follow-up one-to-one interviews. Twenty interviews were completed as data saturation was achieved after the 14th. Interviews were transcribed and analysed using framework methodology as described by Ritchie and Spencer in 1994. Results Survey response rate was 43%. Respondents represented English CPs in terms of age but males and non-whites were over-represented. The majority of CPs accessed SM and MH apps for personal use but did not recommend these in a professional capacity due to lack of awareness and confidentiality/liability concerns. Most would promote an SM health page (78.6%) or MH app (83.7%) if maintained by healthcare professionals (HCPs). Under 35s were more positive about these tools in PH. Two interview themes emerged: The role of CPs in PH; Concerns and opportunities for the use of technology in PH. Conclusions Most CPs, particularly those under 30, were positive about the use of SM and MH apps in PH. Training on the use of such tools among the pharmacy team, and an awareness of the availability of evidence-based apps will ensure their wider adoption.

Background Esophageal Squamous Cell Carcinoma(ESCC) comprises 90% of esophageal cancer worldwide which typically presents at advanced stages and has extremely poor outcomes. Established risk factors for ESCC include tobacco, alcohol and betel nut use. We hypothesized that a screening program for high risk subjects could be established in a low- to middle-income country, using a low-cost, non-endoscopic, retrievable capsule sponge device called EsophaCap(EC). Methods The Institutional Review Board-approved study was conducted in western India from March 2017 through February 2018. Patients with high risk characteristics(smoking, tobacco, betel nut, alcohol, hot beverage consumption) were included. Patients with severe dysphagia, current upper aerodigestive tract cancer, metastatic cancer, esophageal varices, cirrhosis, and portal hypertension were excluded. Following EC specimen retrieval, endoscopic biopsies were collected at 20cm, 30cm and from any visible mucosal abnormalities. Cytology and biopsy specimens underwent H&E staining. An interim analysis was performed to make necessary changes given the lack of baseline data in this field. Results Of the 100 enrolled subjects(85% males, median age 50 years), 93% successfully swallowed the EC and 90% completed endoscopy. The median patient experience score on a 6-point visual analog scale was 5(‘minimal discomfort’). Six(7%) subjects had ESCC on their biopsy. In 2 ESCC patients with mild dysphagia, sponge cytology accurately detected atypical squamous cells(ASC) and dysplasia(100% Sensitivity & Specificity). The other 4 ESCC patients had moderate dysphagia with a near-complete obstruction. In 2 asymptomatic patients with no mucosal abnormalities on endoscopy or biopsies, sponge cytology detected ASC. Longitudinal follow-up of these patients is ongoing. On biopsies from twenty-one(23%) patients, leukoplakia was identified. Conclusion ESCC screening using the EC is feasible with good patient tolerance. Analysis of the cytology samples with H&E staining is potentially accurate for patients with non-obstructive lesions but has a high false negative rate in patients with advanced lesions, when the EC can’t traverse the obstruction. An unusually high rate of leukoplakia was detected in this population and will be evaluated as a potentially pre-malignant lesion with increased risk for development of ESCC. Future studies will include high-throughput sequencing to identify molecular changes that may correspond with leukoplakia or dysplastic cells retrieved with the EC. Disclosure All authors have declared no conflicts of interest.

An effective synthesis which provides facile access to highly rigid tetraazamacrocycles possessing labile functional groups is reported. Essential to the approach is bis-bispidinone, a versatile substrate which can be prepared from an unusually stable bispidine diethyl ketal building block and requires a non-aqueous isolation process. Further functionalization of the substrate allows direct and concurrent incorporation of functionalities onto the bis-bispidine tetraazamacrocyclic framework, in particular those that are labile during the macrocycle formation.

The use of botanical pesticides for protecting crops from insect pests has assumed greater importance all over the world owing to growing awareness of harmful effects of indiscriminate use of synthetic pesticides. Inula racemosa Hook. f. (Asteraceae), a medicinally important perennial herb, is rich in sesquiterpenes with many biological activities. The present studies were conducted with the objective to evaluate the sesquiterpenes isolated from I. racemosa for insecticidal activity against Spodoptera litura (F.).Alantolactone and isoalantolactone isolated from I. racemosa exerted growth inhibitory effects on S. litura. Addition of both the sesquiterpenes to larval diet extended the development period and reduced pupation as well as adult emergence. The dietary utilisation experiments on third-instar larvae of S. litura revealed reduction in consumption and growth rates of larvae as well as efficiency of conversion of ingested and digested food owing to alantolactone and isoalantolactone.The root extract of I. racemosa, which is rich in two sesquiterpenes, i.e. alantolactone and isoalantolactone, has the potential for management of S. litura. However, there is a need to understand the specific mechanism of action of these compounds. © 2016 Society of Chemical Industry.

We report on a case of acute kidney injury in a patient with severe volume depletion from high ileostomy output and poor oral intake associated with hyperuricemia and hyperkalemia. The patient presented with similar features on three separate admissions. A conservative management approach was undertaken that included infusion of rasburicase, since the patient refused to undergo hemodialysis on each occasion. Rasburicase is a recombinant urate oxidase enzyme that converts uric acid to allantoin which is five to ten times more soluble than uric acid in urine, thereby enhancing urinary excretion. Rasburicase was administered each time and was followed by a prompt increase in urine output, rapid decrease in serum uric acid level, and recovery of renal function without the need for acute renal replacement therapy. We believe that rasburicase, with a molecular weight of 34 kDa, crossed the glomerular filtration barrier and entered the tubular fluid where it dissolved intra-tubular uric acid, thus relieving obstruction, thereby rapidly enhancing urine excretion and improving renal function. Based on this experience, we propose that rasburicase offers an alternative treatment for acute kidney injury in similar types of settings. To the best of our knowledge this is the first reported case in this situation.

Sural nerve impingement is frequently reported and often arises from localized trauma but much less understood are its mechanical etiologies. This case report describes the effects of local traction on the lateral calcaneal branch of the sural nerve. The association is confirmed anatomically and symptoms are alleviated with a heel lift. (J Am Podiatr Med Assoc 102(1): 75–77, 2012)

A two-channel long-haul soliton propagation system is demonstrated. Extensive variations of system parameters were numerically studied to provide the optimized system reported. In this system each soliton carries 80 Gb/s pseudo-random bit signal over 14,000 km. Key system parameters, such as the input peak power, the non linear coefficient, average dispersion and the number of sections of fiber in one amplifier length, are optimized, while the Q factor is monitored. As the Q factor falls below the threshold of 6.0 (corresponding to a BER of one error in a billion bits) the propagation distance is noted. For this optimized system a Q-factor threshold distance of 12700 km was obtained. This yields a bit-rate-distance (BL) product in excess of 2 ∙ 1015 b/s km.

A four-channel soliton system design is described that repre-sents an improvement on a previous study Opt. Express , 2007 . In thatstudy, a bit-rate-length BL product in excess of 2.0 1510 baud/kmfrom a dense-dispersion-managed DDM dual-soliton system wasachieved through numerical experimentation. Similar to the dual-solitondesign, a combination of polarization multiplexing and wavelength-division multiplexing is employed. Numerical experiments with four soli-ton channels, each carrying 80 Gb/s, are carried out over 10,000 km.Assystem parameters are optimized, the Q =6 threshold distance attainedis 9150 km, yielding a BL product of 2.9 1510 baud/km. © 2008 Society ofPhoto-Optical Instrumentation Engineers. DOI: 10.1117/1.3027480 Subject terms: soliton; dispersion management; polarization multiplexing;wavelength-division multiplexing . Paper 080241R received Apr. 30, 2008; revised manuscript received Aug. 21,2008; accepted for publication Sep. 23, 2008; published online Dec. 1, 2008.