Paper on a disc: balancing the capillary-driven flow with a centrifugal force

This paper describes the active control of the capillary-driven flow in paper using a centrifugal device.close191

Preclinical Analysis of Irreversible Electroporation on Rat Liver Tissues Using a Microfabricated Electroporator

A microfabricated electroporator (MFE) for the irreversible electroporation (IRE) of tissues has been developed by miniaturizing a clinical electroporator with a two-needle array while keeping the same electric field strength distribution. Since IRE was brought to special attention as one of the local tissue ablation techniques to treat tumors, many preclinical studies have been conducted to investigate the efficacy of IRE on animal tissues. However, some technical difficulties have been frequently encountered due to the macroscale dimension of clinical electroporators, particularly in experiments on small animal models such as the mouse or rat. Here, the MFE was proposed to solve the associated problems, resulting in time-and cost-effective experimental procedures. With the developed MFE, the effect of IRE on rat liver tissues was analyzed with time by immunohistological stainings and electrical measurement, and the experimental results were compared with those operated with the corresponding real-scale clinical electroporator.Choi YS, 2009, ANAL CHEM, V81, P3517, DOI 10.1021/ac900055rMaor E, 2009, PLOS ONE, V4, DOI 10.1371/journal.pone.0004757Pavlin M, 2008, BIOELECTROCHEMISTRY, V74, P38, DOI 10.1016/j.bioelechem.2008.04.016Sersa G, 2008, EJSO-EUR J SURG ONC, V34, P232, DOI 10.1016/j.ejso.2007.05.016Rubinsky B, 2007, TECHNOL CANCER RES T, V6, P255Onik G, 2007, TECHNOL CANCER RES T, V6, P295Al-Sakere B, 2007, TECHNOL CANCER RES T, V6, P301Maor E, 2007, TECHNOL CANCER RES T, V6, P307Garon EB, 2007, INT J CANCER, V121, P675, DOI 10.1002/ijc.22723Esser AT, 2007, TECHNOL CANCER RES T, V6, P261Lee EW, 2007, TECHNOL CANCER RES T, V6, P287Kimelman N, 2007, TISSUE ENG, V13, P1135, DOI 10.1089/ten.2007.0096Lavee J, 2007, HEART SURG FORUM, V10, pE162, DOI 10.1532/HSF98.20061202Rubinsky B, 2007, TECHNOL CANCER RES T, V6, P37Liu L, 2006, CANCER RES, V66, P11851, DOI 10.1158/0008-5472.CAN-06-1377Marty M, 2006, EJC SUPPL, V4, P3, DOI 10.1016/j.ejcsup.2006.08.002Sersa G, 2006, EJC SUPPL, V4, P52, DOI 10.1016/j.ejcsup.2006.08.007Edd JF, 2006, IEEE T BIO-MED ENG, V53, P1409, DOI [10.1109/TBME.2006.873745, 10.1109/TMBE.2006.873745]Miller L, 2005, TECHNOL CANCER RES T, V4, P699Sel D, 2005, IEEE T BIO-MED ENG, V52, P816, DOI 10.1109/TBME.2005.845212Davalos RV, 2005, ANN BIOMED ENG, V33, P223, DOI 10.1007/s10439-005-8981-8Pliquett U, 2004, BIOELECTROCHEMISTRY, V62, P83, DOI 10.1016/j.biolechem.2003.11.001Davalos RV, 2003, BIOELECTROCHEMISTRY, V61, P99, DOI 10.1016/j.bioelechem.2003.07.001Weaver JC, 2003, IEEE T DIELECT EL IN, V10, P754, DOI 10.1109/TDEI.2003.1237325Gothelf A, 2003, CANCER TREAT REV, V29, P371, DOI 10.1016/S0305-7372(03)00073-2Gehl J, 2003, ACTA PHYSIOL SCAND, V177, P437Leu JI, 2003, J CLIN INVEST, V111, P129, DOI 10.1172/JCI200316712Deng ZS, 2001, PHYSICA A, V300, P521Ryttsen F, 2000, BIOPHYS J, V79, P1993Dev SB, 2000, IEEE T PLASMA SCI, V28, P206, DOI 10.1109/27.842905Duffy DC, 1998, ANAL CHEM, V70, P4974Boone K, 1997, J MED ENG TECHNOL, V21, P201Weaver JC, 1996, BIOELECTROCH BIOENER, V41, P135*I LAB AN RES NAT, 1996, GUID CAR US LAB ANABIDOR IG, 1993, BIOCHIM BIOPHYS ACTA, V1152, P207DILLER KR, 1992, MODELING BIOHEAT TRAMIR LM, 1991, CR ACAD SCI III-VIE, V313, P613DUCK FA, 1990, PHYS PROPERTIES ISSUKINOSITA K, 1979, BIOCHIM BIOPHYS ACTA, V554, P479PENNES HH, 1948, J APPL PHYSIOL, V1, P93

Breast Cancer Diagnosis Using a Microfluidic Multiplexed Immunohistochemistry Platform

BACKGROUND: Biomarkers play a key role in risk assessment, assessing treatment response, and detecting recurrence and the investigation of multiple biomarkers may also prove useful in accurate prediction and prognosis of cancers. Immunohistochemistry (IHC) has been a major diagnostic tool to identify therapeutic biomarkers and to subclassify breast cancer patients. However, there is no suitable IHC platform for multiplex assay toward personalized cancer therapy. Here, we report a microfluidics-based multiplexed IHC (MMIHC) platform that significantly improves IHC performance in reduction of time and tissue consumption, quantification, consistency, sensitivity, specificity and cost-effectiveness. METHODOLOGY/PRINCIPAL FINDINGS: By creating a simple and robust interface between the device and human breast tissue samples, we not only applied conventional thin-section tissues into on-chip without any additional modification process, but also attained perfect fluid control for various solutions, without any leakage, bubble formation, or cross-contamination. Four biomarkers, estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2), progesterone receptor (PR) and Ki-67, were examined simultaneously on breast cancer cells and human breast cancer tissues. The MMIHC method improved immunoreaction, reducing time and reagent consumption. Moreover, it showed the availability of semi-quantitative analysis by comparing Western blot. Concordance study proved strong consensus between conventional whole-section analysis and MMIHC (n = 105, lowest Kendall's coefficient of concordance, 0.90). To demonstrate the suitability of MMIHC for scarce samples, it was also applied successfully to tissues from needle biopsies. CONCLUSIONS/SIGNIFICANCE: The microfluidic system, for the first time, was successfully applied to human clinical tissue samples and histopathological diagnosis was realized for breast cancers. Our results showing substantial agreement indicate that several cancer-related proteins can be simultaneously investigated on a single tumor section, giving clear advantages and technical advances over standard immunohistochemical method. This novel concept will enable histopathological diagnosis using numerous specific biomarkers at a time even for small-sized specimens, thus facilitating the individualization of cancer therapy

Staged Surgery for Chronic Primary Aortoduodenal Fistula in a Septic Patient

Aortoenteric fistula is one of the most challenging problems that confront the vascular surgeons. Controversy remains over the optimal treatment because of the continued publication of series with high mortality, amputation, and aortic disruption rates. A positive preoperative blood culture is the best predictor of mortality with increased amputation rates due to infection of the extra-anatomic bypass. Therefore, in selected cases with sepsis, a prudent management protocol is required. We report a 68-yr-old male presenting with a chronic primary aortoduodenal fistula extensively involving the duodenum and Gram-negative sepsis. We planned a staged operation. Initially, an emergency laparotomy and control of the aorta allowed stabilization of the patient, identification of the fistula, and direct in situ placement of the prosthetic graft followed by an en bloc resection of the aneurysm and the surrounding structures. After he recovered from sepsis and had been stabilized, a staged extra-anatomic bypass followed by transabdominal removal of the temporarily placed graft was done. This management plan will allow the highest success rate and may be a prudent management protocol for these difficult cases

Targeted mutagenesis in mouse cells and embryos using an enhanced prime editor

Prime editors, novel genome-editing tools consisting of a CRISPR-Cas9 nickase and an engineered reverse transcriptase, can induce targeted mutagenesis. Nevertheless, much effort is required to optimize and improve the efficiency of prime-editing. Herein, we introduce two strategies to improve the editing efficiency using proximal dead sgRNA and chromatin-modulating peptides. We used enhanced prime-editing to generate Igf2 mutant mice with editing frequencies of up to 47% and observed germline transmission, no off-target effects, and a dwarf phenotype. This improved prime-editing method can be efficiently applied to cell research and to generate mouse models.This study was supported by the Chung Yang, Cha Young Sun, & Jang Hi Joo Memorial Fund. This study was also supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) of Korea (Korea Mouse Phenotyping Project, NRF-2013M3A9D5072550, NRF-2020M3A9D5A01082439, NRF2019R1A2C2087198, and NRF- 2019M3A9H1103792)

Elevated red cell distribution width is associated with advanced fibrosis in NAFLD

Background/AimsThe red-blood-cell distribution width (RDW) is a newly recognized risk marker in patients with cardiovascular disease, but its role in nonalcoholic fatty liver disease (NAFLD) has not been well defined. The aim of the present study was to determine the association between RDW values and the level of fibrosis in NAFLD according to BARD and FIB-4 scores.MethodsThis study included 24,547 subjects who had been diagnosed with NAFLD based on abdominal ultrasonography and questionnaires about alcohol consumption. The degree of liver fibrosis was determined according to BARD and FIB-4 scores. The association between RDW values and the degree of fibrosis in NAFLD was analyzed retrospectively.ResultsAfter adjusting for age, hemoglobin level, mean corpuscular volume, history of hypertension, history of diabetes, and high-sensitivity C-reactive protein, the RDW values were 12.61±0.41% (mean±SD), 12.70±0.70%, 12.77±0.62%, 12.87±0.82%, and 13.25±0.90% for those with BARD scores of 0, 1, 2, 3, and 4, respectively, and 12.71±0.72%, 12.79±0.66%, and 13.23±1.52% for those with FIB-4 scores of <1.30, 1.31-2.66, and ≥2.67, respectively (P<0.05). The prevalence of advanced fibrosis (BARD score of 24 and FIB-4 score of ≥1.3) increased with the RDW [BARD score: 51.1% in quartile 1 (Q1) vs. 63.6% in Q4; FIB-4 score: 6.9% in Q1 vs. 10.5% in Q4; P<0.001]. After adjustments, the odds ratio of having advanced fibrosis for those in Q4 compared to Q1 were 1.76 (95%CI=1.55-2.00, P<0.001) relative to BARD score and 1.69 (95%CI=1.52-1.98, P<0.001) relative to FIB-4 score.ConclusionsElevated RDW is independently associated with advanced fibrosis in NAFLD

The Clinical Outcome of FLAG Chemotherapy without Idarubicin in Patients with Relapsed or Refractory Acute Myeloid Leukemia

A refractory and resistant disease to conventional induction chemotherapy and relapsed disease are considered as the most important adverse prognostic factors for acute myeloid leukemia (AML). Sixty-one patients (median age, 33.6 yr) with relapsed or refractory AML were treated with the FLAG regimen that consisted of fludarabine (30 mg/m2, days 1-5), cytarabine (2.0 g/m2, days 1-5) and granulocyte colony-stimulating factor. Of the treated patients 29 patients (47.5%) achieved complete remission (CR). Higher CR rates were observed for patients with a first or second relapse as compared to patients with a primary refractory response or relapse after stem cell transplantation (HSCT). There was a significant difference in the response rates according to the duration of leukemia-free survival (pre-LFS) before chemotherapy (P=0.05). The recovery time of both neutrophils (≥500/µL) and platelets (≥20,000/µL) required a median of 21 and 18 days, respectively. Treatment-related mortality (TRM) occurred in seven patients (11.4%), of which 71.4% of TRM was caused by an invasive aspergillosis infection. After achieving CR, 18 patients underwent consolidation chemotherapy and six patients underwent allogeneic HSCT. In conclusion, FLAG chemotherapy without idarubicin is a relatively effective and well-tolerated regimen for relapsed or refractory AML and the use of FLAG chemotherapy has allowed intensive post-remission therapy including HSCT

Prognostic significance of a systemic inflammatory response in patients receiving first-line palliative chemotherapy for recurred or metastatic gastric cancer

<p>Abstract</p> <p>Background</p> <p>There is increasing evidence that the presence of an ongoing systemic inflammatory response is associated with poor prognosis in patients with advanced cancers. We evaluated the relationships between clinical status, laboratory factors and progression free survival (PFS), and overall survival (OS) in patients with recurrent or metastatic gastric cancer receiving first-line palliative chemotherapy.</p> <p>Methods</p> <p>We reviewed 402 patients with advanced gastric adenocarcinoma who received first-line palliative chemotherapy from June 2004 and December 2009. Various chemotherapy regimens were used. Eastern Cooperative Oncology Group performance status (ECOG PS), C-reactive protein (CRP), albumin, Glasgow prognostic score (GPS), and clinical factors were recorded immediately prior to first-line chemotherapy. Patients with both an elevated CRP (>1.0 mg/dL) and hypoalbuminemia (<3.5 mg/dL) were assigned a GPS of 2. Patients in whom only one of these biochemical abnormalities was present were assigned a GPS of 1, and patients with a normal CRP and albumin were assigned a score of 0. To evaluate the factors that affected PFS and OS, univariate and multivariate analyses were performed.</p> <p>Results</p> <p>According to multivariate analysis, the factors independently associated with PFS were ECOG PS (HR 1.37, 95% CI 1.02-1.84, <it>P </it>= 0.035), bone metastasis (HR 1.74, 95% CI 1.14-2.65, <it>P </it>= 0.009), and CRP elevation (HR 1.64, 95% CI 1.28-2.09, <it>P </it>= 0.001). The factors independently associated with OS were ECOG PS (HR 1.33, 95% CI 1.01-1.76, <it>P </it>= 0.037), bone metastasis (HR 1.61, 95% CI 1.08-2.39, <it>P </it>= 0.017), and GPS ≥ 1 (HR 1.76, 95% CI 1.41-2.19, <it>P </it>= 0.001).</p> <p>Conclusions</p> <p>The results of this study showed that the presence of a systemic inflammatory response as evidenced by the CRP, GPS was significantly associated with shorter PFS and OS in patients with recurrent or metastatic gastric cancer receiving first-line palliative chemotherapy. Bone metastasis and GPS were very useful indicator for survival in patients with recurrent or metastatic gastric cancer receiving palliative chemotherapy.</p

Generation of homogeneous midbrain organoids with in vivo-like cellular composition facilitates neurotoxin-based Parkinson\u27s disease modeling

Recent studies have demonstrated the generation of midbrain-like organoids (MOs) from human pluripotent stem cells. However, the low efficiency of MO generation and the relatively immature and heterogeneous structures of the MOs hinder the translation of these organoids from the bench to the clinic. Here we describe the robust generation of MOs with homogeneous distribution of midbrain dopaminergic (mDA) neurons. Our MOs contain not only mDA neurons but also other neuronal subtypes as well as functional glial cells including astrocytes and oligodendrocytes. Furthermore, our MOs exhibit mDA neuron-specific cell death upon treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, indicating that MOs could be a proper human model system for studying the in vivo pathology of Parkinson\u27s disease (PD). Our optimized conditions for producing homogeneous and mature MOs might provide an advanced patient-specific platform for in vitro disease modeling as well as for drug screening for PD