Determination of Optimal Cell and Plasmid Concentration for Transfection of I-SceI by DR-GFP Reporter

https://openworks.mdanderson.org/sumexp21/1195/thumbnail.jp

Type and dose of radiotherapy used for initial treatment of non-metastatic prostate cancer

BACKGROUND: We sought to describe patterns of initial radiotherapy among non-metastatic prostate cancer (PC) patients by recurrence risk groups. METHODS: Medical records were abstracted for a sample of 9017 PC cases diagnosed in 2004 as a part of the Center for Disease Control and Prevention\u27s Prostate and Breast Patterns of Care Study in seven states. Non-metastatic PC cases are categorized as low-risk (LR), intermediate-risk (IR) or high-risk (HR) groups based on pretreatment PSA, tumor stage, and Gleason score per 2002 NCCN guidelines. Univariate and multivariate analyses were employed to determine factors associated with the type and dose of radiotherapy by the risk groups. RESULTS: Of the 9,017 patients, 3153 who received definitive radiotherapy either alone or in combination with hormone therapy (HT) were selected for in-depth analysis. Multivariate models showed that LR patients were more likely to receive seed implant brachytherapy (BT) than those in higher risk groups. Those in the IR group were most likely to receive external beam radiotherapy (EBRT) combined with BT or high-dose radiotherapy. Use of HT in combination with radiotherapy was more common in the IR and HR groups than for LR patients. Intensity modulated radiation treatment (IMRT) was used to treat 32.6% of PC patients treated with EBRT, with the majority (60.6%) treated with high-dose radiotherapy. CONCLUSIONS: Radiotherapy types and dosage utilization varied by PC risk groups. Patients in IR were more likely than those in LR or HR to receive high-dose radiotherapy. IMRT was used in about one third of patients to deliver high-dose radiotherapy

Standing Balance and Spatiotemporal Aspects of Gait Are Impaired Upon Nocturnal Awakening in Healthy Late Middle-Aged and Older Adults

Study Objectives: Nocturnal awakenings may constitute a unique risk for falls among older adults. We describe differences in gait and balance between presleep and midsleep testing, and whether changes in the lighting environment during the midsleep testing further affect gait and balance. Methods: Twenty-one healthy, late middle-aged and older (64.7 ± 8.0 y) adults participated in this repeated-measures design consisting of four overnight laboratory stays. Each night, participants completed baseline visual acuity, gait, and balance testing. After a 2-h sleep opportunity, they were awakened for 13 min into one of four lighting conditions: very dim white light (\u3c 0.5 lux); dim white light (∼28.0 lux); dim orange light (∼28.0 lux); and white room-level light (∼200 lux). During this awakening, participants completed the same sequence of testing as at baseline. Results: Low-contrast visual acuity significantly decreased with decreasing illuminance conditions (F(3,45) = 98.26, p \u3c 0.001). Our a priori hypothesis was confirmed in that variation in stride velocity and center of pressure path length were significantly worse during the mid-sleep awakening compared to presleep baseline. Lighting conditions during the awakening, however, did not influence these parameters. In exploratory analyses, we found that over one-third of the tested gait and balance parameters were significantly worse at the midsleep awakening as compared to baseline (p \u3c 0.05), and nearly one-quarter had medium to large effect sizes (Cohen d ≥ 0.5; r ≥ 0.3). Conclusions: Balance and gait are impaired during midsleep awakenings among healthy, late middle-aged and older adults. This impairment is not ameliorated by exposure to room lighting, when compared to dim lights

A Single-Cell Level and Connectome-Derived Computational Model of the Drosophila Brain

Computer simulations play an important role in testing hypotheses, integrating knowledge, and providing predictions of neural circuit functions. While considerable effort has been dedicated into simulating primate or rodent brains, the fruit fly (Drosophila melanogaster) is becoming a promising model animal in computational neuroscience for its small brain size, complex cognitive behavior, and abundancy of data available from genes to circuits. Moreover, several Drosophila connectome projects have generated a large number of neuronal images that account for a significant portion of the brain, making a systematic investigation of the whole brain circuit possible. Supported by FlyCircuit (http://www.flycircuit.tw), one of the largest Drosophila neuron image databases, we began a long-term project with the goal to construct a whole-brain spiking network model of the Drosophila brain. In this paper, we report the outcome of the first phase of the project. We developed the Flysim platform, which (1) identifies the polarity of each neuron arbor, (2) predicts connections between neurons, (3) translates morphology data from the database into physiology parameters for computational modeling, (4) reconstructs a brain-wide network model, which consists of 20,089 neurons and 1,044,020 synapses, and (5) performs computer simulations of the resting state. We compared the reconstructed brain network with a randomized brain network by shuffling the connections of each neuron. We found that the reconstructed brain can be easily stabilized by implementing synaptic short-term depression, while the randomized one exhibited seizure-like firing activity under the same treatment. Furthermore, the reconstructed Drosophila brain was structurally and dynamically more diverse than the randomized one and exhibited both Poisson-like and patterned firing activities. Despite being at its early stage of development, this single-cell level brain model allows us to study some of the fundamental properties of neural networks including network balance, critical behavior, long-term stability, and plasticity

Postchemoradiotherapy Pathologic Stage Classified by the American Joint Committee on the Cancer Staging System Predicts Prognosis of Patients with Locally Advanced Esophageal Squamous Cell Carcinoma

IntroductionTo determine whether the postchemoradiotherapy (post-CRT) pathologic stage predicts the outcomes of patients with locally advanced esophageal squamous cell carcinoma (ESCC) undergoing preoperative CRT followed by surgery.MethodsFrom three phase II trials of preoperative CRT for locally advanced ESCC, 140 patients were included. Preoperative CRT comprised twice weekly paclitaxel and cisplatin-based regimens and 40-Gy radiotherapy in 20 fractions. The post-CRT pathologic stage was classified according to the American Joint Committee on Cancer, 7th edition staging system. The prognostic effects of clinicopathologic factors were analyzed using Cox regression.ResultsWith a median follow-up of 61.9 months, the median progression-free survival (PFS) and overall survival (OS) of the entire cohort were 24.5 and 30.9 months, respectively. The post-CRT pathologic stage was 0 in 34.5%, I in 12.9%, II in 29.3%, III in 13.6%, and ypT0N1-2 in 6.4% of the patients. The median PFS was 47.2, 25.9, 16.0, 9.4, and 15.1 months, and the median OS was 57.4, 34.1, 26.2, 14.1, and 17.6 months for patients with post-CRT pathologic stage 0, I, II, III, and ypT0N1-2, respectively. In multivariate analysis, performance status (p < 0.001), tumor location (p = 0.016), and extranodal extension (p = 0.024) were independent prognostic factors for PFS, whereas performance status (p < 0.001) and post-CRT pathologic stage (p = 0.027) were independent prognostic factors for OS.ConclusionsThe post-CRT pathologic stage classified by American Joint Committee on Cancer, 7th edition staging system predicted the survival of locally advanced ESCC patients who underwent preoperative paclitaxel and cisplatin-based CRT followed by esophagectomy

Solitary fibrous tumour of the genitourinary tract: a clinicopathological study of 11 cases and their association with the NAB2-STAT6 fusion gene

Aims To characterise clinicopathological features and clinical outcomes of the genitourinary tract solitary fibrous tumours, incorporating NAB2-STAT6 gene fusion status. Methods The presence of the molecular hallmark NAB2-STAT6 gene fusion and for the defining fusion partner product STAT6 was assessed in 11 cases of the genitourinary tract solitary fibrous tumours. NAB2-STAT6 gene fusion analysis was performed using a break-apart fluorescence in situ hybridisation (FISH) probe using a probe cocktail with Bacterial artificial chromosome (BAC) clones for STAT6 and NAB2. Results Eleven solitary fibrous tumours were diagnosed in eight male patients and three female patients with a mean age of 46 years (range: 11–64 years). Four of the tumours had malignant histological features, and three were considered moderate risk for metastasis. With a mean follow-up time of 61 months, 1 recurred locally and 2 presented at distant metastatic sites. Using a break-apart FISH probe cocktail, we found the NAB2-STAT6 gene fusion and nuclear STAT6 expression in 58% and 91% of cases, respectively. However, the NAB2-STAT6 fusion status was not correlated with STAT6 expression or useful in discriminating between malignant histological features or subsequent clinical outcomes in the genitourinary solitary fibrous tumours. Conclusions A subset of solitary fibrous tumours of the genitourinary tract behaved aggressively. Using a break-apart FISH probe cocktail, we found the NAB2-STAT6 gene fusion in 64% of cases. However, the NAB2-STAT6 fusion status was not correlated with STAT6 expression or useful in discriminating between low-risk or high-risk tumours and subsequent clinical outcomes

PP1 Forms an Active Complex with TLRR (lrrc67), a Putative PP1 Regulatory Subunit, during the Early Stages of Spermiogenesis in Mice

Mammalian spermatogenesis is a highly regulated developmental pathway that demands dramatic rearrangement of the cytoskeleton of the male germ cell. We have described previously a leucine rich repeat protein, TLRR (also known as lrrc67), which is associated with the spermatid cytoskeleton in mouse testis and is a binding partner of protein phosphatase-1 (PP1), an extremely well conserved signaling molecule. The activity of PP1 is modulated by numerous specific regulators of which TLRR is a candidate. In this study we measured the phosphatase activity of the TLRR-PP1 complex in the adult and the developing mouse testis, which contains varying populations of developing germ cell types, in order to determine whether TLRR acts as an activator or an inhibitor of PP1 and whether the phosphatase activity of this complex is developmentally regulated during spermatogenesis. Additionally, we assayed the ability of bacterially expressed TLRR to affect the enzymatic activity of PP1. Furthermore, we examined phosphorylation of TLRR, and elements of the spermatid cytoskeleton during the first wave of spermatogenesis in the developing testis. We demonstrate here that the TLRR complex is associated with a phosphatase activity in adult mouse testis. The relative phosphatase activity of this complex appears to reach a peak at about 21 days after birth, when pachytene spermatocytes and round spermatids are abundant in the seminiferous epithelium of the mouse testis. TLRR, in addition to tubulin and kinesin-1B, is phosphorylated during the first wave of spermatogenesis. These findings indicate that the TLRR-PP1 complex is active prior to translocation of TLRR toward the sperm flagella and that TLRR, and constituents of the spermatid cytoskeleton, may be subject to regulation by reversible phosphorylation during spermatogenesis in murine testis