Thin Film Composite Silicon Elastomers for Cell Culture and Skin Applications: Manufacturing and Characterization

A protocol for the manufacturing process of polymeric thin film composite structures possessing either different Young's moduli or thicknesses is presented. Films are produced for advanced cell culture studies or as skin adhesives.

https://ift.tt/2lSjgki

Generation of Size-controlled Poly (ethylene Glycol) Diacrylate Droplets via Semi-3-Dimensional Flow Focusing Microfluidic Devices

Here, we present a protocol to illustrate the fabrication processes and verifying experiments of a semi-three-dimensional (semi-3D) flow-focusing microfluidic chip for droplet formation.

https://ift.tt/2u0Fg05

Multidimensional analyses reveal distinct immune microenvironment in hepatitis B virus-related hepatocellular carcinoma

Background and aims

Chronic inflammation induced by chronic hepatitis B virus (HBV) infection increases the risk of hepatocellular carcinoma (HCC). However, little is known about the immune landscape of HBV-related HCC and its influence on the design of effective cancer immunotherapeutics.

Methods

We interrogated the immune microenvironments of HBV-related HCC and non-viral-related HCC using immunohistochemistry and ytometry by time-of-flight (CyTOF). On identifying unique immune subsets enriched in HBV-related HCC, we further interrogated their phenotypes and functions using next-generation sequencing (NGS) and in vitro T-cell proliferation assays.

Results

In-depth interrogation of the immune landscapes showed that regulatory T cells (T_REG) and CD8⁺ resident memory T cells (T_RM) were enriched in HBV-related HCC, whereas Tim-3⁺CD8⁺ T cells and CD244⁺ natural killer cells were enriched in non-viral-related HCC. NGS of isolated T_REG and T_RM from HBV-related HCC and non-viral-related HCC identified distinct functional signatures associated with T-cell receptor signalling, T-cell costimulation, antigen presentation and programmed cell death protein 1 (PD-1) signalling. T_REG and T_RM from HBV-related HCC expressed more PD-1 and were functionally more suppressive and exhausted than those from non-virus-related HCC. Furthermore, immunosuppression by PD-1⁺ T_REG could be reversed with anti-PD-1 blockade. Using multiplexed tissue immunofluorescence, we further demonstrated that T_REG and T_RM contributed to overall patient survival: T_REG were associated with a poor prognosis and T_RM were associated with a good prognosis in HCC.

Conclusion

We have shown that the HBV-related HCC microenvironment is more immunosuppressive and exhausted than the non-viral-related HCC microenvironment. Such in-depth understanding has important implications in disease management and appropriate application of immunotherapeutics.

https://ift.tt/2MMREZA

Health-Related Quality of Life among Women Breast Cancer Patients in Eastern China

Objectives. Breast cancer is one of the major cancers in Chinese women. European Organization for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ-C30 and QLQ-BR23) are now the most common and well developed instruments assessing the health-related quality of life (HRQOL) of breast cancer patients internationally, whereas there are relatively few Chinese studies. This study has two aims: to investigate the HRQOL and explore which dimensions of HRQOL play more important roles in breast cancer patients' overall quality of life in China and to explore the latent factor structure and the potential complementary relationship between these two EORTC questionnaires. Methods. This cross-sectional and descriptive study was performed from October 2014 to February 2015 in Qingdao Municipal Hospital, China. A total of 621 women breast cancer patients were enrolled. EOTRC QLQ-C30 and QLQ-BR23 were used to evaluate the HRQOL of the participants. The nonparametric test, multiple linear regression, and exploratory factor analysis (EFA) were the main statistical methods we used. Results. 608 participants completed the questionnaires with a response rate of 97.9%. The mean age of the participants was 48.0 years (SD=9.6). About 33% were illiterate or only finished primary school education. Almost half participants (47.4%) only adopted chemotherapy. HRQOL was significantly different with regard to patients' social-demographic and clinical characteristics. Age, residence, educational level, employment status, and TNM stage were five significant predictors for global health status. Pain, dyspnea, sexual enjoyment, and systemic therapy side-effect were main subscales which had a significant impact on the global health status for patients in different TNM stage. The EFA result suggested that QLQ-C30 and QLQ-BR23 were complementary questionnaires. Conclusions. The EORTC QLQ-C30 and QLQ-BR23 questionnaires provide complementary information regarding breast cancer patients' HRQOL, and depending on the different cancer staging functional/symptom scales which significantly contributed to the overall HRQOL differed.

https://ift.tt/2lVGt5r

In vitro leishmanicidal effects of the anti-fungal drug natamycin are mediated through disruption of calcium homeostasis and mitochondrial dysfunction

Abstract

Natamycin, a Food and Drug Administration approved anti-fungal drug, and also used as a food additive was evaluated for anti-leishmanial activity since it is known to specifically bind to ergosterol, which is essential to these parasites but absent in mammals. Promising anti-proliferative activity was observed in both promastigote and amastigote forms of the parasite with IC₅₀ values of 15 and 8 µM respectively and a selective index of 12.5. The ultrastructural effects of natamycin on both forms of the parasite and physiological effects on promastigotes were studied in detail for the first time. Electron microscopic observations in treated cells revealed sub-cellular changes like plasma membrane alterations, accumulation of vesicles in the flagellar pocket and extensive mitochondrial damage. Natamycin treatment in promastigotes resulted in elevation of cytosolic calcium (Ca²⁺) levels which caused irreversible loss of mitochondrial membrane potential. This resulted in depletion of cellular ATP levels along with ROS generation finally leading to apoptosis-like and necrotic cell death. In view of our observations along with the safety profile of an existing anti-fungal drug, natamycin may be further investigated for repurposing it as a promising drug candidate against Leishmaniasis.

https://ift.tt/2KH23Iz

CC Nerd-The Case of the Neutral Documents

A brief editorial aside: Both Josh and Scott have commented on the BICAR-ICU Trial in previous posts, each presenting well thought out erudite analyses. I recommend reading/listening to them. EMCrit: Acid Base Episode 7 PulmCrit: pH-guided fluid resuscitation & BICAR-ICU The overwhelming need for euboxia has inspired a multitude of therapeutic endeavors, including the use of […]

EMCrit Project by Rory Spiegel.

https://ift.tt/2IPDX9H

Non-invasive kinetic modelling of PET tracers with radiometabolites using a constrained simultaneous estimation method: evaluation with 11 C-SB201745

Abstract

Background

Kinetic analysis of dynamic PET data requires an accurate knowledge of available PET tracer concentration within blood plasma over time, known as the arterial input function (AIF). The gold standard method used to measure the AIF requires serial arterial blood sampling over the course of the PET scan, which is an invasive procedure and makes this method less practical in clinical settings. Traditional image-derived methods are limited to specific tracers and are not accurate if metabolites are present in the plasma.

Results

In this work, we utilise an image-derived whole blood curve measurement to reduce the computational complexity of the simultaneous estimation method (SIME), which is capable of estimating the AIF directly from tissue time activity curves (TACs). This method was applied to data obtained from a serotonin receptor study (¹¹C-SB207145) and estimated parameter results are compared to results obtained using the original SIME and gold standard AIFs derived from arterial samples. Reproducibility of the method was assessed using test-retest data. It was shown that the incorporation of image-derived information increased the accuracy of total volume of distribution (V _T) estimates, averaged across all regions, by 40% and non-displaceable binding potential (BP _ND) estimates by 16% compared to the original SIME. Particular improvements were observed in K₁ parameter estimates. BP _ND estimates, based on the proposed method and the gold standard arterial sample-derived AIF, were not significantly different (P=0.7).

Conclusions

The results of this work indicate that the proposed method with prior AIF information obtained from a partial volume corrected image-derived whole blood curve, and modelled parent fraction, has the potential to be used as an alternative non-invasive method to perform kinetic analysis of tracers with metabolite products.

https://ift.tt/2lRTRHJ