Zoning of mucosal phenotype, dysplasia, and telomerase activity measured by telomerase repeat assay protocol in Barrett's esophagus

Glandular dysplasia in Barrett's esophagus may regress spontaneously but can also progress to cancer. The human telomerase RNA template and the human telomerase reverse transcriptase enzyme which do not, of themselves, correlate strongly with telomerase activity, are too often overexpressed in Barrett's dysplasia to predict individual cancer risk. This study relates telomerase activity, mucosal phenotype, and dysplasia in Barrett's esophagus. Biopsies (n = 256) from squamous esophagus, columnar-lined esophagus every 2 cm, esophago-gastric junction, gastric body, and antrum from 32 patients with long-segment Barrett's esophagus were evaluated by telomerase repeat assay protocol (TRAP). Three biopsies for histology (n = 794) were simultaneously taken at each anatomical level. These and all prior and subsequent biopsies (n = 1917) were reviewed for mucosal phenotypes and dysplasia severity. Intestinal-type Barrett's mucosa was present at all levels in Barrett's esophagus. At least one Barrett's biopsy was TRAP(+) in 22 of 32 patients. TRAP positivity of intestinal-type Barrett's mucosa increased distally, possibly as a consequence of mucosal exposure to acid or bile reflux. Native gastric mucosa was rarely TRAP(+) (1/31 corpus, 2/32 antrum), whereas native squamous mucosa usually was TRAP(+) (31/32). Dysplasia almost always involved intestinal-type Barrett's mucosa (85/87; P</p

Pulsar Results with the Fermi Large Area Telescope

The launch of the Fermi Gamma-ray Space Telescope has heralded a new era in the study of gamma-ray pulsars. The population of confirmed gamma-ray pulsars has gone from 6-7 to more than 60, and the superb sensitivity of the Large Area Telescope (LAT) on Fermi has allowed the detailed study of their spectra and light curves. Twenty-four of these pulsars were discovered in blind searches of the gamma-ray data, and twenty-one of these are, at present, radio quiet, despite deep radio follow-up observations. In addition, millisecond pulsars have been confirmed as a class of gamma-ray emitters, both individually and collectively in globular clusters. Recently, radio searches in the direction of LAT sources with no likely counterparts have been highly productive, leading to the discovery of a large number of new millisecond pulsars. Taken together, these discoveries promise a great improvement in the understanding of the gamma-ray emission properties and Galactic population of pulsars. We summarize some of the results stemming from these newly-detected pulsars and their timing and multi-wavelength follow-up observations.Comment: 21 pages, 9 figures, to appear in Proceedings of ICREA Workshop on The High-Energy Emission from Pulsars and their Systems, Sant Cugat, Spain, 2010 April 12-16 (Springer

Surgical physiology of inguinal hernia repair - a study of 200 cases

BACKGROUND: Current inguinal hernia operations are generally based on anatomical considerations. Failures of such operations are due to lack of consideration of physiological aspects. Many patients with inguinal hernia are cured as a result of current techniques of operation, though factors that are said to prevent hernia formation are not restored. Therefore, the surgical physiology of inguinal canal needs to be reconsidered. METHODS: A retrospective study is describer of 200 patients operated on for inguinal hernia under local anaesthesia by the author's technique of inguinal hernia repair. RESULTS: The posterior wall of the inguinal canal was weak and without dynamic movement in all patients. Strong aponeurotic extensions were absent in the posterior wall. The muscle arch movement was lost or diminished in all patients. The movement of the muscle arch improved after it was sutured to the upper border of a strip of the external oblique aponeurosis (EOA). The newly formed posterior wall was kept physiologically dynamic by the additional muscle strength provided by external oblique muscle to the weakened muscles of the muscle arch. CONCLUSIONS: A physiologically dynamic and strong posterior inguinal wall, and the shielding and compression action of the muscles and aponeuroses around the inguinal canal are important factors that prevent hernia formation or hernia recurrence after repair. In addition, the squeezing and plugging action of the cremasteric muscle and binding effect of the strong cremasteric fascia, also play an important role in the prevention of hernia

Pathologies in Asymptotically Lifshitz Spacetimes

There has been significant interest in the last several years in studying possible gravitational duals, known as Lifshitz spacetimes, to anisotropically scaling field theories by adding matter to distort the asymptotics of an AdS spacetime. We point out that putative ground state for the most heavily studied example of such a spacetime, that with a flat spatial section, suffers from a naked singularity and further point out this singularity is not resolvable by any known stringy effect. We review the reasons one might worry that asymptotically Lifshitz spacetimes are unstable and employ the initial data problem to study the stability of such systems. Rather surprisingly this question, and even the initial value problem itself, for these spacetimes turns out to generically not be well-posed. A generic normalizable state will evolve in such a way to violate Lifshitz asymptotics in finite time. Conversely, enforcing the desired asymptotics at all times puts strong restrictions not just on the metric and fields in the asymptotic region but in the deep interior as well. Generically, even perturbations of the matter field of compact support are not compatible with the desired asymptotics.Comment: 36 pages, 1 figure, v2: Enhanced discussion of singularity, including relationship to Gubser's conjecture and singularity in RG flow solution, plus minor clarification

Chemical combination effects predict connectivity in biological systems

Efforts to construct therapeutically useful models of biological systems require large and diverse sets of data on functional connections between their components. Here we show that cellular responses to combinations of chemicals reveal how their biological targets are connected. Simulations of pathways with pairs of inhibitors at varying doses predict distinct response surface shapes that are reproduced in a yeast experiment, with further support from a larger screen using human tumour cells. The response morphology yields detailed connectivity constraints between nearby targets, and synergy profiles across many combinations show relatedness between targets in the whole network. Constraints from chemical combinations complement genetic studies, because they probe different cellular components and can be applied to disease models that are not amenable to mutagenesis. Chemical probes also offer increased flexibility, as they can be continuously dosed, temporally controlled, and readily combined. After extending this initial study to cover a wider range of combination effects and pathway topologies, chemical combinations may be used to refine network models or to identify novel targets. This response surface methodology may even apply to non-biological systems where responses to targeted perturbations can be measured

Prospective blind comparative clinical study of two point fixation of zygomatic complex fracture using wire and mini plates

<p>Abstract</p> <p>Background</p> <p>The zygomatic maxillary complex (ZMC) fractures are one of the most frequent injuries of the facial skeleton due to its position and facial contour. Assaults, road traffic accidents and falls are the principal etiologic factors that may cause fractures of zygomatic bone. The different fixation methods are applied to treat the zygomatic bone fractures, with many more classifications which have been described in the literature for the ease of management. The type of the fracture, its severity and associated facial fractures usually interferes the treatment modality.</p> <p>Purpose of study</p> <p>The aim of this paper is to show the results of 18yrs prospective blind comparative study using wire and plate osteosynthesis which needed open reduction and internal fixation involving Type II to Type IV Spissel and Schroll ZMC fractures.</p> <p>Materials and methods</p> <p>Total 80 cases included in the study out of 1780 ZMC cases which were treated using wire and plate osteosynthesis over a period of 18 yrs, involving only Type II to Type IV Spissel and Schroll ZMC fractures. Other types excluded from study to prevent observer bias. All the fixations carried out through Standard Dingman's incision using stainless steel 26 gauze wire and titanium 1.5 mm mini plate system under general anesthesia by single maxillofacial surgeon and evaluated by another maxillofacial surgeon who is blinded for surgical procedure after 2 and 4 wks of follow-up for facial symmetry, wound healing, functional assessment (mouth opening, diplopia), and sensory disturbance. All the data tabulated in Excel software (Microsoft) for statistical analysis. P-value calculated to know the Significance of treatment modality in all aspects.</p> <p>Results</p> <p>Result shows no significant p-values indicating both the operating techniques are equally efficient in the surgical management of ZMC fracture.</p> <p>Conclusion</p> <p>Osteosynthesis by mini plates is simple, logical and effective treatment compared to wire osteosynthesis in regard to stability of fracture fragments. Wire osteosynthesis will be helpful in emergency surgeries or where the mini plates are not available. Even though the wire osteosynthesis is economical compared to mini plate fixation; but the time and skill is required for fixation of wires.</p

Advanced optical imaging in living embryos

Developmental biology investigations have evolved from static studies of embryo anatomy and into dynamic studies of the genetic and cellular mechanisms responsible for shaping the embryo anatomy. With the advancement of fluorescent protein fusions, the ability to visualize and comprehend how thousands to millions of cells interact with one another to form tissues and organs in three dimensions (xyz) over time (t) is just beginning to be realized and exploited. In this review, we explore recent advances utilizing confocal and multi-photon time-lapse microscopy to capture gene expression, cell behavior, and embryo development. From choosing the appropriate fluorophore, to labeling strategy, to experimental set-up, and data pipeline handling, this review covers the various aspects related to acquiring and analyzing multi-dimensional data sets. These innovative techniques in multi-dimensional imaging and analysis can be applied across a number of fields in time and space including protein dynamics to cell biology to morphogenesis

Histone deacetylases as new therapy targets for platinum-resistant epithelial ovarian cancer

Introduction: In developed countries, ovarian cancer is the fourth most common cancer in women. Due to the nonspecific symptomatology associated with the disease many patients with ovarian cancer are diagnosed late, which leads to significantly poorer prognosis. Apart from surgery and radiotherapy, a substantial number of ovarian cancer patients will undergo chemotherapy and platinum based agents are the mainstream first-line therapy for this disease. Despite the initial efficacy of these therapies, many women relapse; therefore, strategies for second-line therapies are required. Regulation of DNA transcription is crucial for tumour progression, metastasis and chemoresistance which offers potential for novel drug targets. Methods: We have reviewed the existing literature on the role of histone deacetylases, nuclear enzymes regulating gene transcription. Results and conclusion: Analysis of available data suggests that a signifant proportion of drug resistance stems from abberant gene expression, therefore HDAC inhibitors are amongst the most promising therapeutic targets for cancer treatment. Together with genetic testing, they may have a potential to serve as base for patient-adapted therapies

Locomotor adaptation to a powered ankle-foot orthosis depends on control method

<p>Abstract</p> <p>Background</p> <p>We studied human locomotor adaptation to powered ankle-foot orthoses with the intent of identifying differences between two different orthosis control methods. The first orthosis control method used a footswitch to provide bang-bang control (a kinematic control) and the second orthosis control method used a proportional myoelectric signal from the soleus (a physiological control). Both controllers activated an artificial pneumatic muscle providing plantar flexion torque.</p> <p>Methods</p> <p>Subjects walked on a treadmill for two thirty-minute sessions spaced three days apart under either footswitch control (n = 6) or myoelectric control (n = 6). We recorded lower limb electromyography (EMG), joint kinematics, and orthosis kinetics. We compared stance phase EMG amplitudes, correlation of joint angle patterns, and mechanical work performed by the powered orthosis between the two controllers over time.</p> <p>Results</p> <p>During steady state at the end of the second session, subjects using proportional myoelectric control had much lower soleus and gastrocnemius activation than the subjects using footswitch control. The substantial decrease in triceps surae recruitment allowed the proportional myoelectric control subjects to walk with ankle kinematics close to normal and reduce negative work performed by the orthosis. The footswitch control subjects walked with substantially perturbed ankle kinematics and performed more negative work with the orthosis.</p> <p>Conclusion</p> <p>These results provide evidence that the choice of orthosis control method can greatly alter how humans adapt to powered orthosis assistance during walking. Specifically, proportional myoelectric control results in larger reductions in muscle activation and gait kinematics more similar to normal compared to footswitch control.</p