Identifying Biomagnetic Sources in the Brain by the Maximum Entropy Approach

Magnetoencephalographic (MEG) measurements record magnetic fields generated from neurons while information is being processed in the brain. The inverse problem of identifying sources of biomagnetic fields and deducing their intensities from MEG measurements is ill-posed when the number of field detectors is far less than the number of sources. This problem is less severe if there is already a reasonable prior knowledge in the form of a distribution in the intensity of source activation. In this case the problem of identifying and deducing source intensities may be transformed to one of using the MEG data to update a prior distribution to a posterior distribution. Here we report on some work done using the maximum entropy method (ME) as an updating tool. Specifically, we propose an implementation of the ME method in cases when the prior contain almost no knowledge of source activation. Two examples are studied, in which part of motor cortex is activated with uniform and varying intensities, respectively.Comment: 8 pages, 8 figures. Presented at 25th International Workshop on Bayesian Inference and Maximum Entropy Methods in Science and Engineering, San Jose, CA, USA Aug 7-12, 200

Delivery of chemotherapeutic agents using drug-loaded irradiated tumor cells to treat murine ovarian tumors

<p>Abstract</p> <p>Background</p> <p>Ovarian cancer is the leading cause of death among women with gynecologic malignancies in the United States. Advanced ovarian cancers are difficult to cure with the current available chemotherapy, which has many associated systemic side effects. Doxorubicin is one such chemotherapeutic agent that can cause cardiotoxicity. Novel methods of delivering chemotherapy without significant side effects are therefore of critical need.</p> <p>Methods</p> <p>In the current study, we generated an irradiated tumor cell-based drug delivery system which uses irradiated tumor cells loaded with the chemotherapeutic drug, doxorubicin.</p> <p>Results</p> <p>We showed that incubation of murine ovarian cancer cells (MOSEC) with doxorubicin led to the intracellular uptake of the drug (MOSEC-dox cells) and the eventual death of the tumor cell. We then showed that doxorubicin loaded MOSEC-dox cells were able to deliver doxorubicin to MOSEC cells in vivo. Further characterization of the doxorubicin transfer revealed the involvement of cell contact. The irradiated form of the MOSEC-dox cells were capable of treating luciferase-expressing MOSEC tumor cells (MOSEC/luc) in C57BL/6 mice as well as in athymic nude mice resulting in improved survival compared to the non drug-loaded irradiated MOSEC cells. Furthermore, we showed that irradiated MOSEC-dox cells was more effective compared to an equivalent dose of doxorubicin in treating MOSEC/luc tumor-bearing mice.</p> <p>Conclusions</p> <p>Thus, the employment of drug-loaded irradiated tumor cells represents a potentially innovative approach for the delivery of chemotherapeutic drugs for the control of ovarian tumors.</p

Femtosecond laser treatment enhances DNA transfection efficiency in vivo

<p>Abstract</p> <p>Background</p> <p>Gene therapy with plasmid DNA is emerging as a promising strategy for the treatment of many diseases. One of the major obstacles to such therapy is the poor transfection efficiency of DNA <it>in vivo</it>.</p> <p>Methods</p> <p>In this report, we employed a very low power, near-infrared femtosecond laser technique to enhance the transfection efficiency of intradermally and intratumorally administered DNA plasmid.</p> <p>Results</p> <p>We found that femtosecond laser treatment can significantly enhance the delivery of DNA into the skin and into established tumors in mice. In addition, we found that both laser power density as well as duration of laser treatment are critical parameters for augmenting DNA transfection efficiency. The femtosecond laser technique employs a relatively unfocused laser beam that maximizes the transfected area, minimizes damage to tissue and simplifies its implementation.</p> <p>Conclusion</p> <p>This femtosecond new laser technology represents a safe and innovative technology for enhancing DNA gene transfer in vivo.</p

Neoadjuvant Carboplatin/Paclitaxel versus 5-Fluorouracil/Cisplatin in Combination with Radiotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma:A Multicenter Comparative Study

SIMPLE SUMMARY: The most beneficial neoadjuvant chemoradiotherapy for Asian patients with esophageal squamous cell carcinoma remains uncertain. Using propensity score matching by inverse probability of treatment weighting to balance the baseline variables, the neoadjuvant carboplatin/paclitaxel (CROSS) regimen versus the cisplatin/5-fluorouracil (PF) regimen in combination with 41.4–50.4 Gy of radiotherapy were compared. We found that Taiwanese patients treated with the CROSS regimen (Carboplatin + Paclitaxel + 41.4–45.0 Gy) had less treatment-related complications and more favorable survival figures. Collectively, these results suggest that CROSS is safe and effective. ABSTRACT: Background: The most beneficial neoadjuvant chemoradiotherapy (nCRT) combination for esophageal squamous cell carcinoma (ESCC) in Asia remains uncertain. Herein, we compared the neoadjuvant carboplatin/paclitaxel (CROSS) regimen versus the cisplatin/5-fluorouracil (PF) regimen in combination with 41.4–50.4 Gy of radiotherapy. Methods: Patients were stratified according to their nCRT regimen: CROSS + 41.4–45.0 Gy (CROSS), PF + 45.0 Gy (PF4500) or PF + 50.4 Gy (PF5040). Propensity score matching by inverse probability of treatment weighting (IPTW) was used to balance the baseline variables. Results: Before IPTW, a total of 334 patients were included. The lowest chemotherapy completion rate was observed in the PF5040 group (76.2% versus 89.4% and 92.0% in the remaining two groups, respectively). Compared with CROSS, both PF groups showed more severe weight loss during nCRT and a higher frequency of post-esophagectomy anastomotic leaks. The use of PF5040 was associated with the highest rate of pathological complete response (45.3%). While CROSS conferred a significant overall survival benefit over PF4500 (hazard ratio [HR] = 1.30, 95% CI = 1.05 to 1.62, p = 0.018), similar survival figures were observed when compared with PF5040 (HR = 1.17, 95% CI = 0.94 to 1.45, p = 0.166). Conclusions: The CROSS regimen conferred a significant survival benefit over PF4500, although the similar survival figures were similar to those observed with PF5040. Considering the lower incidences of severe weight loss and post-esophagectomy anastomotic leaks, CROSS represents a safe and effective neoadjuvant treatment for Taiwanese patients with ESCC

The need for nursing instruction in patients receiving steroid pulse therapy for the treatment of autoimmune diseases and the effect of instruction on patient knowledge

<p>Abstract</p> <p>Background</p> <p>Many patients who receive steroid pulse therapy go home the same day or the day after steroid administration. Nursing instructions are important for improving patient knowledge related to their diseases and treatments, but the short hospital stay often prevents complete education and guidance regarding the given therapy. The purpose of this study was to investigate the need for nursing instruction in patients receiving steroid pulse therapy for the treatment of autoimmune diseases and the effect of instruction on patient knowledge of their disease and treatment.</p> <p>Methods</p> <p>Patients with systemic lupus erythematosus (SLE) and systemic sclerosis receiving steroid pulse therapy (N = 63) were recruited from a medical center in Taipei. A structured questionnaire was used for data collection before and after nursing instruction, and 1 week as well as 2 weeks after therapy. The need for nursing instruction and knowledge levels were validated using Cronbach's α reliability test.</p> <p>Results</p> <p>There was a significant difference (<it>P </it>< 0.001) in the need for nursing instruction among the 4 time points. There was a positive correlation between the need for nursing instruction and body weight change, frequency of treatment, and distress, but there was a negative correlation with knowledge level (β = -0.012, <it>P </it>= 0.003) regarding symptoms. The knowledge level of subjects after nursing instruction was significantly higher than before nursing instruction (80 ± 14.31 vs. 70.06 ± 17.23, <it>P </it>< 0.001).</p> <p>Conclusions</p> <p>This study indicates that nursing instruction is needed by patients receiving steroid pulse therapy, and that by designing and administering nursing instructions according to the priority of patient symptoms, nurses can improve patient knowledge related to their diseases and treatments. In addition, the need for nursing instruction can be affected by patient characteristics.</p

Constitutive Expression of Thermobifida fusca Thermostable Acetylxylan Esterase Gene in Pichia pastoris

A gene encoding the thermostable acetylxylan esterase (AXE) in Thermobifida fusca NTU22 was amplified by PCR, sequenced and cloned into the Pichia pastoris X-33 host strain using the vector pGAPZαA, allowing constitutive expression and secretion of the protein. Recombinant expression resulted in high levels of extracellular AXE production, as high as 526 U/mL in the Hinton flask culture broth. The purified enzyme showed a single band at about 28 kDa by SDS-polyacrylamide gel electrophoresis after being treated with endo-β-N-acetylglycosaminidase H; this agrees with the predicted size based on the nucleotide sequence. About 70% of the original activity remained after heat treatment at 60 °C for three hours. The optimal pH and temperature of the purified enzyme were 8.0 and 60 °C, respectively. The properties of the purified AXE from the P. pastoris transformant are similar to those of the AXE from an E. coli transformant

Use of Ceftriaxone in Treating Cognitive and Neuronal Deficits Associated With Dementia With Lewy Bodies

Dementia with Lewy bodies (DLB) is caused by accumulation of Lewy bodies, destruction of mitochondria, and excess of glutamate in synapses, which eventually leads to excitotoxicity, neurodegeneration, and cognitive impairments. Ceftriaxone (CEF) reduces excitotoxicity by increasing glutamate transporter 1 expression and glutamate reuptake. We investigated whether CEF can prevent cognitive decline and neurological deficits and increase neurogenesis in DLB rats. Male Wistar rats infused with viral vector containing human alpha-synuclein (α-syn) gene, SNCA, in the lateral ventricle were used as a rat model of DLB. CEF (100 mg/kg/day, i.p.) was injected in these rats for 27 days. The active avoidance test and object recognition test was performed. Finally, the brains of all the rats were immunohistochemically stained to measure α-syn, neuronal density, and newborn cells in the hippocampus and substantia nigra. The results revealed that DLB rats had learning and object recognition impairments and exhibited cell loss in the nigrostriatal dopaminergic system, and hippocampal CA1, and dentate gyrus (DG). Additionally, DLB rats had fewer newborn cells in the DG and substantia nigra pars reticulata and more α-syn immune-positive cells in the DG. Treatment with CEF improved cognitive function, reduced cell loss, and increased the number of newborn cells in the brain. To our knowledge, this is the first study showing that CEF prevents loss of neurogenesis in the brain of DLB rats. CEF may therefore has clinical potential for treating DLB

Assessing trends and predictors of tuberculosis in Taiwan

<p>Abstract</p> <p>Background</p> <p>Variety of environmental and individual factors can cause tuberculosis (TB) incidence change. The purpose of this study was to assess the characteristics of TB trends in the period 2004 - 2008 in Taiwan by month, year, gender, age, temperature, seasonality, and aborigines.</p> <p>Methods</p> <p>The generalized regression models were used to examine the potential predictors for the monthly TB incidence in regional and national scales.</p> <p>Results</p> <p>We found that (<it>i</it>) in Taiwan the average TB incidence was 68 per 100,000 population with mortality rate of 0.036 person^-1yr^-1, (<it>ii</it>) the highest TB incidence rate was found in eastern Taiwan (116 per 100,000 population) with the largest proportion of TB relapse cases (8.17%), (<it>iii</it>) seasonality, aborigines, gender, and age had a consistent and dominant role in constructing TB incidence patterns in Taiwan, and (<it>iv</it>) gender, time trend, and 2-month lag maximum temperature showed strong association with TB trends in aboriginal subpopulations.</p> <p>Conclusions</p> <p>The proposed Poisson regression model is capable of forecasting patterns of TB incidence at regional and national scales. This study suggested that assessment of TB trends in eastern Taiwan presents an important opportunity for understanding the time-series dynamics and control of TB infections, given that this is the typical host demography in regions where these infections remain major public health problems.</p