Human red blood cell behaviour under homogeneous extensional flow in a hyperbolic-shaped microchannel

It is well known that certain pathological conditions result in a decrease of red blood cells (RBCs) deformability and subsequently can significantly alter the blood flow in microcirculation, which may block capillaries and cause ischemia in the tissues. Microfluidic systems able to obtain reliable quantitative measurements of RBC deformability hold the key to understand and diagnose RBC related diseases. In this work, a microfluidic system composed of a microchannel with a hyperbolic-shaped contraction followed by a sudden expansion is presented. We provide a detailed quantitative description of the degree of deformation of human RBCs under a controlled homogeneous extensional flow field. We measured the deformation index (DI) as well as the velocity of the RBCs travelling along the center line of the channel for four different flow rates and analyze the impact of the particle Reynolds number. The results show that human RBC deformation tends to reach a plateau value in the region of constant extensional rate, the value of which depends on the extension rate. Additionally, we observe that the presence of a sudden expansion downstream of the hyperbolic contraction modifies the spatial distribution of cells and substantially increases the cell free layer (CFL) downstream of the expansion plane similarly to what is seen in other expansion flows. Beyond a certain value of flow rate, there is only a weak effect of inlet flow rates on the enhancement of the downstream CFL. These in vitro experiments show the potential of using microfluidic systems with hyperbolic-shaped microchannels both for the separation of the RBCs from plasma and to assess changes in RBC deformability in physiological and pathological situations for clinical purposes. However, the selection of the geometry and the identification of the most suitable region to evaluate the changes on the RBC deformability under extensional flows are crucial if microfluidics is to be used as an in vitro clinical methodology to detect circulatory diseases

The Japanese model in retrospective : industrial strategies, corporate Japan and the 'hollowing out' of Japanese industry

This article provides a retrospective look at the Japanese model of industrial development. This model combined an institutional approach to production based around the Japanese Firm (Aoki's, J-mode) and strategic state intervention in industry by the Japanese Ministry of International Trade and Industry (MITI). For a long period, the alignment of state and corporate interests appeared to match the wider public interest as the Japanese economy prospered. However, since the early 1990s, the global ambitions of the corporate sector have contributed to a significant 'hollowing out' of Japan's industrial base. As the world today looks for a new direction in economic management, we suggest the Japanese model provides policy-makers with a salutary lesson in tying the wider public interest with those of the corporate sector

Dry Bacterial Cellulose and Carboxymethyl Cellulose formulations with interfacial-active performance: processing conditions and redispersion

Dry or powdered formulations of food additives facilitate transportation, storage, preservation and handling. In this work, dry formulations of bacterial cellulose and carboxymethyl cellulose (BC:CMC), easily redispersible and preserving the functionality of the never-dried dispersions are reported. Different processing parameters and their effect on the materials properties were evaluated, namely: (i) wet-grinding of BC (Hand-blender, Microcut Head Impeller, High-pressure Homogenizer), (ii) drying of BC:CMC mixtures (fast drying at130 °C and slow drying at 80 °C) and subsequent (iii) comminution to different particle sizes. The dispersibility of the obtained BC:CMC powders was evaluated, and their functionality after redispersion was assessed by measuring the dynamic viscosity, the effect in oil/water interfacial tension (liquidliquid system) and the stabilization of cocoa in milk (solidliquid system). The size of BC fibre bundles was of paramount relevance to its stabilizing ability in multiphasic systems. A more extensive wet-grinding of the BC fibres was accompanied by a loss in the BC:CMC functionality, related to the increasingly smaller size of the BC bundles. Indeed, as the Dv (50) of the wet BC bundles was reduced from 1228 to 55 µm, the BC:CMC viscosity profile dropped and the effect on interfacial tension decreased. This effect was observed both on the never-dried and dry BC:CMC formulations. On the other hand, the drying method did not play a major effect in the materials properties. In a benchmarking study, the BC:CMC formulations, at a low concentration (0.15%), had better stabilizing ability of the cocoa particles than several commercial cellulose products.Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10570-020-03211-9) contains supplementary material, which is available to authorized users.This study was supported by FCT under the scope of the strategic funding of UID/BIO/04469/2019 unit and BioTecNorte operation (NORTE-01-0145-FEDER000004) funded by the European Regional Development Fund under the scope of Norte2020-Programa Operacional Regional do Norte. Daniela Martins also gratefully acknowledges FCT for the PhD scholarship, reference SFRH/BD/115917/2016.info:eu-repo/semantics/publishedVersio

Infective endocarditis with Lactococcus garvieae in Japan: a case report

<p>Abstract</p> <p>Introduction</p> <p><it>Lactococcus garvieae </it>is a well-recognized fish pathogen, and it is considered a rare pathogen with low virulence in human infection. We describe the 11th case of <it>L. garvieae </it>infective endocarditis reported in the literature, and the first reported case in Japan.</p> <p>Case presentation</p> <p>We report a case of a 55-year-old Japanese woman who had native valve endocarditis with <it>L. garvieae</it>. The case was complicated by renal infarction, cerebral infarction, and mycotic aneurysms. After anti-microbial treatment, she was discharged from the hospital and is now well while being monitored in the out-patient clinic.</p> <p>Conclusion</p> <p>We encountered a case of <it>L. garvieae </it>endocarditis that occurred in a native valve of a healthy woman. The 16S ribosomal RNA gene sequencing was useful for the identification of this pathogen. Although infective endocarditis with <it>L. garvieae </it>is uncommon, it is possible to treat high virulence clinically.</p

Gene therapy for carcinoma of the breast: Therapeutic genetic correction strategies

Gene therapy is a therapeutic approach that is designed to correct specific molecular defects that contribute to the cause or progression of cancer. Genes that are mutated or deleted in cancers include the cancer susceptibility genes p53 and BRCA1. Because mutational inactivation of gene function is specific to tumor cells in these settings, cancer gene correction strategies may provide an opportunity for selective targeting without significant toxicity for normal nontumor cells. Both p53 and BRCA1 appear to inhibit cancer cells that lack mutations in these genes, suggesting that the so-called gene correction strategies may have broader potential than initially believed. Increasing knowledge of cancer genetics has identified these and other genes as potential targets for gene replacement therapy. Initial patient trials of p53 and BRCA1 gene therapy have provided some indications of potential efficacy, but have also identified areas of basic and clinical research that are needed before these approaches may be widely used in patient care

Gene-specific repair of Pt/DNA lesions and induction of apoptosis by the oral platinum drug JM216 in three human ovarian carcinoma cell lines sensitive and resistant to cisplatin

JM216, an oral platinum drug entering into phase III clinical trial, exhibited comparable cytotoxicity to cisplatin in three human ovarian carcinoma cell lines: the sensitive (CH1), acquired resistant (CH1cisR) and intrinsically resistant (SKOV-3). Platinum accumulation and binding to DNA were similar in each of the three cell lines at equimolar doses, indicating that the resistant cell lines could tolerate higher intracellular platinum levels and platinum bound to DNA at IC50 concentrations of drug. Comparison with cisplatin demonstrated that intracellular platinum levels were marginally higher with JM216, but that platinum binding to DNA was similar for the two drugs in each of the cell lines. Each of the cell lines exhibited an ability to repair JM216 induced platinum/DNA lesions in the N-ras gene (gene-specific repair) at equitoxic concentrations of drug. However, this occurred to a greater extent in the two resistant cell lines such that by 24 h the CH1cisR and SKOV-3 had removed 72% and 67% respectively compared with approximately 32% for the CH1. Reduced gene-specific repair capacity in CH1 cells was also seen following incubation with 25 μM (or 5 μM – 2 × IC50) cisplatin, whereas the CH1cisR and SKOV-3 cell lines were repair proficient. JM216 induced apoptosis in the three cell lines following a 2h incubation with 2 × the IC50 of drug. Fluorescent microscopy of cells stained with propidium iodide showed that the detached cell population displayed typical apoptotic nuclei. Furthermore, field inversion gel electrophoresis demonstrated the presence of DNA fragments approximately 23–50 kb in size, indicative of apoptosis, in the detached cells. JM216 induced an S phase slow down in each of the three cell lines accompanied by a G2 block in the CH1 pair. Incubation with this concentration of JM216 also resulted in the induction of p53 in the CH1 and CH1cisR. These studies suggest that the relative sensitivity of the CH1 cell line to cisplatin and JM216 is at least partly attributable to a deficiency in gene-specific repair. The oral platinum drug, JM216, exerts its cytotoxic effects through the induction of apoptosis following a slow-down in S phase in both the sensitive and resistant lines. © 1999 Cancer Research Campaig