ROCK Inhibitor Is Not Required for Embryoid Body Formation from Singularized Human Embryonic Stem Cells

We report a technology to form human embryoid bodies (hEBs) from singularized human embryonic stem cells (hESCs) without the use of the p160 rho-associated coiled-coil kinase inhibitor (ROCKi) or centrifugation (spin). hEB formation was tested under four conditions: +ROCKi/+spin, +ROCKi/-spin, -ROCKi/+spin, and -ROCKi/-spin. Cell suspensions of BG01V/hOG and H9 hESC lines were pipetted into non-adherent hydrogel substrates containing defined microwell arrays. hEBs of consistent size and spherical geometry can be formed in each of the four conditions, including the -ROCKi/-spin condition. The hEBs formed under the -ROCKi/-spin condition differentiated to develop the three embryonic germ layers and tissues derived from each of the germ layers. This simplified hEB production technique offers homogeneity in hEB size and shape to support synchronous differentiation, elimination of the ROCKi xeno-factor and rate-limiting centrifugation treatment, and low-cost scalability, which will directly support automated, large-scale production of hEBs and hESC-derived cells needed for clinical, research, or therapeutic applications

Improved Measurement of Electron Antineutrino Disappearance at Daya Bay

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Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

The efficacy of four-slice helical CT in evaluating pancreatic trauma: a single institution experience

<p>Abstract</p> <p>Study objective</p> <p>To assess the efficacy of computed tomography (CT) in evaluating patients with pancreatic trauma.</p> <p>Methods</p> <p>We undertook a retrospective review of all blunt trauma patients admitted to the Chi-Mei Medical Center from January 2004 to June 2006. Every patients underwent abdominal CT scan in emergency department and the CT scans were obtained with a four-slice helical CT. Diagnosis of a pancreatic injury in these patients was by surgical observation or by CT findings. Radiographic pancreatic injuries were classified as deep or superficial lesions. Deep lesions were defined as the hematomas or lacerations >50% thickness of the pancreas. Superficial lesions were described as the hematomas or lacerations <50% thickness of the pancreas; pancreatic edema; and focal fluid accumulation around the pancreas</p> <p>Results</p> <p>Nineteen patients with pancreatic trauma, fourteen males and five females, average age 40.6 ± 21.4 years, were included. Most patients (73.7%) with pancreatic trauma had associated organ injuries. CT was performed in all patients and laparotomy in 14 patients. CT was 78.9% sensitive in detecting pancreatic trauma. All deep pancreatic lesions revealed on CT required surgical treatment, and complication was discovered in two patients undergoing delayed surgery. Superficial lesions were managed conservatively.</p> <p>Conclusion</p> <p>Four-slice helical CT can detect most pancreatic trauma and provide practical therapeutic guidance. Delayed operation might result in complications and is associated with prolonged hospital stays.</p

Cancer risk from gaseous carbonyl compounds in indoor environment generated from household coal combustion in Xuanwei, China

Airborne carbonyls were characterized from emitted indoor coal combustion. Samples were collected in Xuanwei (Yunnan Province), a region in China with a high rate of lung cancer. Eleven of 19 types of samples (58%) demonstrated formaldehyde concentrations higher than the World Health Organization exposure limit (a 30-min average of 100 μg m−3). Different positive significant correlations between glyoxal/methylglyoxal and formaldehyde/acetaldehyde concentrations were observed, suggesting possible different characteristics in emissions between two pairs of carbonyl compounds. A sample in the highest inhalation risk shows 29.2 times higher risk than the lowest sample, suggesting different coal sampling locations could contribute to the variation of inhalation risk. Inhabitants in Xuanwei also tend to spend more time cooking and more days per year indoors than the national average. The calculated cancer risk ranged from 2.2–63 × 10−5, which shows 13 types of samples at high-risk level. Cumulative effect in combination with different carbonyls could have contributed to the additive actual inhalation cancer risk. There is a need to explicitly address the health effects of environmentally relevant doses, considering life-long exposure in indoor dwellings

Computationally-Optimized Bone Mechanical Modeling from High-Resolution Structural Images

Image-based mechanical modeling of the complex micro-structure of human bone has shown promise as a non-invasive method for characterizing bone strength and fracture risk in vivo. In particular, elastic moduli obtained from image-derived micro-finite element (μFE) simulations have been shown to correlate well with results obtained by mechanical testing of cadaveric bone. However, most existing large-scale finite-element simulation programs require significant computing resources, which hamper their use in common laboratory and clinical environments. In this work, we theoretically derive and computationally evaluate the resources needed to perform such simulations (in terms of computer memory and computation time), which are dependent on the number of finite elements in the image-derived bone model. A detailed description of our approach is provided, which is specifically optimized for μFE modeling of the complex three-dimensional architecture of trabecular bone. Our implementation includes domain decomposition for parallel computing, a novel stopping criterion, and a system for speeding up convergence by pre-iterating on coarser grids. The performance of the system is demonstrated on a dual quad-core Xeon 3.16 GHz CPUs equipped with 40 GB of RAM. Models of distal tibia derived from 3D in-vivo MR images in a patient comprising 200,000 elements required less than 30 seconds to converge (and 40 MB RAM). To illustrate the system's potential for large-scale μFE simulations, axial stiffness was estimated from high-resolution micro-CT images of a voxel array of 90 million elements comprising the human proximal femur in seven hours CPU time. In conclusion, the system described should enable image-based finite-element bone simulations in practical computation times on high-end desktop computers with applications to laboratory studies and clinical imaging

Deep sequencing reveals the complex and coordinated transcriptional regulation of genes related to grain quality in rice cultivars

<p>Abstract</p> <p>Background</p> <p>Milling yield and eating quality are two important grain quality traits in rice. To identify the genes involved in these two traits, we performed a deep transcriptional analysis of developing seeds using both massively parallel signature sequencing (MPSS) and sequencing-by-synthesis (SBS). Five MPSS and five SBS libraries were constructed from 6-day-old developing seeds of Cypress (high milling yield), LaGrue (low milling yield), Ilpumbyeo (high eating quality), YR15965 (low eating quality), and Nipponbare (control).</p> <p>Results</p> <p>The transcriptomes revealed by MPSS and SBS had a high correlation co-efficient (0.81 to 0.90), and about 70% of the transcripts were commonly identified in both types of the libraries. SBS, however, identified 30% more transcripts than MPSS. Among the highly expressed genes in Cypress and Ilpumbyeo, over 100 conserved <it>cis </it>regulatory elements were identified. Numerous specifically expressed transcription factor (TF) genes were identified in Cypress (282), LaGrue (312), Ilpumbyeo (363), YR15965 (260), and Nipponbare (357). Many key grain quality-related genes (i.e., genes involved in starch metabolism, aspartate amino acid metabolism, storage and allergenic protein synthesis, and seed maturation) that were expressed at high levels underwent alternative splicing and produced antisense transcripts either in Cypress or Ilpumbyeo. Further, a time course RT-PCR analysis confirmed a higher expression level of genes involved in starch metabolism such as those encoding ADP glucose pyrophosphorylase (AGPase) and granule bound starch synthase I (GBSS I) in Cypress than that in LaGrue during early seed development.</p> <p>Conclusion</p> <p>This study represents the most comprehensive analysis of the developing seed transcriptome of rice available to date. Using two high throughput sequencing methods, we identified many differentially expressed genes that may affect milling yield or eating quality in rice. Many of the identified genes are involved in the biosynthesis of starch, aspartate family amino acids, and storage proteins. Some of the differentially expressed genes could be useful for the development of molecular markers if they are located in a known QTL region for milling yield or eating quality in the rice genome. Therefore, our comprehensive and deep survey of the developing seed transcriptome in five rice cultivars has provided a rich genomic resource for further elucidating the molecular basis of grain quality in rice.</p