Extended thromboprophylaxis following colorectal surgery in patients with inflammatory bowel disease: a comprehensive systematic clinical review.

AIM: Patients with inflammatory bowel disease (IBD) are at increased risk of postoperative venous thromboembolism (VTE) following major abdominal surgery. The pathogenesis is multifactorial and not fully understood. A combination of pathophysiology, patient and surgical risk factors increase the risk of postoperative VTE in these patients. Despite being at increased risk, IBD patients are not regularly prescribed extended pharmacological thromboprophylaxis following colorectal surgery. Currently, there is a paucity of evidence-based guidelines. Thus, the aim of this review is to evaluate the role of extended pharmacological thromboprophylaxis in IBD patients undergoing colorectal surgery. METHOD: A search of Ovid Medline, EMBASE and PubMed databases was performed. A qualitative analysis was performed using 10 clinical questions developed by colorectal surgeons and a thrombosis haematologist. The Newcastle-Ottawa Scale was utilized to assess the quality of evidence. RESULTS: A total of 1229 studies were identified, 38 of which met the final inclusion criteria (37 retrospective, one case-control). Rates of postoperative VTE ranged between 0.6% and 8.9%. Patient-specific risk factors for postoperative VTE included ulcerative colitis, increased age and obesity. Surgery-specific risk factors for postoperative VTE included open surgery, emergent surgery and ileostomy creation. Patients with IBD were more frequently at increased risk in the included studies for postoperative VTE than patients with colorectal cancer. The risk of bias assessment demonstrated low risk of bias in patient selection and comparability, with variable risk of bias in reported outcomes. CONCLUSION: There is a lack of evidence regarding the use of extended pharmacological thromboprophylaxis in patients with IBD following colorectal surgery. As these patients are at heightened risk of postoperative VTE, future study and consideration of the use of extended pharmacological thromboprophylaxis is warranted.

Clinical challenges in patients with cancer-associated thrombosis: Canadian expert consensus recommendations.

Venous thromboembolism is a common complication in cancer patients, and thromboembolism is the second most common cause of death after cancer progression. A number of clinical practice guidelines provide recommendations for the management of cancer-associated thrombosis. However, the guidelines lack recommendations covering commonly encountered clinical challenges (for example, thrombocytopenia, recurrent venous thromboembolism, etc.) for which little or no evidence exists. Accordingly, recommendations were developed to provide expert guidance to medical oncologists and other health care professionals caring for patients with cancer-associated thrombosis. The current expert consensus was developed by a team of 21 clinical experts. For each identified clinical challenge, the literature in medline, embase, and Evidence Based Medicine Reviews was systematically reviewed. The quality of the evidence was assessed, summarized, and graded. Consensus statements were generated, and the experts voted anonymously using a modified Delphi process on their level of agreement with the various statements. Statements were progressively revised through separate voting iterations and were then finalized. Clinicians using these recommendations and suggestions should tailor patient management according to the risks and benefits of the treatment options, patient values and preferences, and local cost and resource allocations.

A scalable scanning transfer cavity laser stabilization scheme based on the Red Pitaya STEMlab platform.

Many experiments in atomic and molecular physics require simultaneous frequency stabilization of multiple lasers. We present a stabilization scheme based on a scanning transfer cavity lock that is simple, stable, and easily scalable to many lasers at minimal cost. The scheme is based on the Red Pitaya STEMlab platform, with custom software developed and implemented to achieve up to 100 Hz bandwidth. As an example demonstration, we realize simultaneous stabilization of up to four lasers and a reduction of long-term drifts to well below 1 MHz/h. This meets typical requirements, e.g., for experiments on laser cooling of molecules.

Effect of thiazolidinedione treatment on proteinuria and renal hemodynamic in type 2 diabetic patients with overt nephropathy.

Proteinuria in diabetic nephropathy predicts the progressive loss of glomerular filtration rate (GFR) and serves as independent predictor for mortality. We performed the present study (ClinicalTrials.gov identifier: NCT 00324675) to clarify whether the activation of PPARγ receptor by thiazolidinediones was able to improve proteinuria and preserve renal function in advanced diabetic nephropathy. A total of 28 type 2 diabetic patients (4 women and 24 men, mean age 66.1±9.1 years) with urinary albumin excretion >300 mg/24 h and an estimated GFR <60 ml/min were included into this prospective double blind trial to receive either rosiglitazone (RSG) 4 mg b.i.d or matching placebo (PLC) for 52 weeks in addition to their concomitant antidiabetic background therapy. At baseline and after 26 and 52 weeks, renal plasma flow (RPF) and GFR were determined before and after blockade of nitric oxide (NO) by intravenous administration of N-monomethyl-L-arginine acetate. RSG treatment resulted in a significant reduction of proteinuria (2.4±1.1; 1.2±0.6; 1.5±0.7 g/d at baseline, 26 weeks and 52 weeks; respectively, p<0.05) whereas PLC did not influence proteinuria (1.6±0.6; 1.6±0.8; 1.7±0.8 g/d). GFR and RPF did not change significantly during the study, however, RSG improved the intrarenal NO bioavailability. RSG treatment was generally well tolerated and the major adverse event - development of edema - could be controlled by dose adjustment of the study drug and diuretic agents. In conclusion, we demonstrated a possible renoprotective effect of RSG in patients with advanced diabetic nephropathy.

In situ visualization of damaged DNA in human sperm by Raman microspectroscopy.

BACKGROUND: Beyond determining the percentage of damaged sperm, current methods of DNA assessment are of limited clinical utility as they render the sample unusable. We evaluated Raman microspectroscopy, a laser-based non-invasive technique that provides detailed chemical 'fingerprints' of cells and which potentially could be used for nuclear DNA-based sperm selection. METHODS: Eight healthy donors provided ejaculates. After system optimization, a minimum of 200 air-dried sperm/sample/donor, prior to/and after UVB irradiation, were assessed by two observers. Spectra were analysed by Principal Component, Spectral Angle and Wavelet Analyses. RESULTS: Spectra provided a chemical map delineating each sperm head region. Principal Component Analysis showed clear separation between spectra from UV-irradiated and untreated samples whilst averaged data identified two regions of interest (1040 and 1400 cm(-1)). Local spectral analysis around the DNA PO(4) backbone peak (1042 cm(-1)), showed that changes in this region were indicative of DNA damage. Wavelet decomposition confirmed both the 1042 cm(-1) shift and a second UVB susceptible region (1400-1600 cm(-1)) corresponding to protein-DNA interactions. No difference was found between observer measurements. CONCLUSIONS: Raman microspectroscopy can provide accurate and reproducible assessment of sperm DNA structure and the sites and location of damage.

Beam position stabilization for a confocal multiphoton microscope.

The influence of beam-pointing on scanning confocal microscopy is investigated. The beam displacement is measured using a quadrant photodiode, and the apparent movement of a sub-micron-sized particle observed by second-harmonic microscopy is linked to the beam displacement. A simple beam-pointing stabilization is implemented, and improvement of beam stability by three orders of magnitude on long time scales is achieved.

Frequency control of a 1163 nm singly resonant OPO based on MgO:PPLN.

We report the realization of a singly resonant optical parametric oscillator (SRO) that is designed to provide narrow-bandwidth, continuously tunable radiation at a wavelength of 1163 nm for optical cooling of osmium ions. The SRO is based on periodically poled, magnesium-oxide-doped lithium niobate and pumped at 532 nm. The output coupling of the resonant idler wave is adjusted to yield up to 400 mW of 1163 nm radiation, with a bandwidth of a few megahertz. For continuous frequency tuning of the idler wave, the SRO is equipped with an intracavity etalon, and the cavity length is controlled with a piezo-actuated mirror synchronized to the etalon angle.

Fatty acids as metabolic mediators in innate immunity.

BACKGROUND: Increasing data support the hypothesis of a local and systemic crosstalk between adipocytes and monocytes mediated by fatty acids. The aim of this study was to characterize the immunomodulatory effects of a large panel of fatty acids on cytokines and chemokines in monocytic THP-1 cells and primary human monocytes. We tested whether anti-inflammatory fatty acids are able to inhibit the binding of lipopolysaccharide (LPS) to its receptor, toll-like receptor/MD-2 (TLR4/MD-2). MATERIALS AND METHODS: Resistin, monocyte chemoattractant protein-1 (MCP-1) and tumour necrosis factor (TNF) were measured by enzyme-linked immunosorbent assay. Proteins were analysed by Western blot. A designed Flag-tagged TLR4/MD-2 fusion protein (LPS trap) was used to investigate the effect of fatty acids on binding of LPS to its receptor. In 30 patients with type 2 diabetes mellitus (T2D), the correlation of serum triglyceride levels with LPS-induced monocyte activation was analysed. RESULTS: Eleven fatty acids investigated exerted differential effects on the monocytic release of cytokines and chemokines. Eicosapentaenoic acid had potent anti-inflammatory effects on human primary monocytes and THP-1 cells; 100 and 200 microM eicosapentaenoic acid dose-dependently inhibited LPS binding to the LPS trap. LPS-induced release of monocytic MCP-1 and TNF was significantly and positively correlated with serum triglyceride levels in 30 patients with T2D. CONCLUSIONS: Monocytic activation is differentially regulated by fatty acids and depends on triglyceride levels in T2D. The main finding of the present study shows that eicosapentaenoic acid inhibits the specific binding of LPS to TLR4/MD-2. Eicosapentaenoic acid represents a new anti-inflammatory LPS-antagonist.

The effect of protein synthesis inhibition on the entry of messenger RNA into the cytoplasm of sea urchin embryos.

Emetine is a potent inhibitor of protein synthesis in sea urchin embryos. At a concentration of the drug that rapidly inhibits protein synthesis in blastulae by 95%, uridine incorporation into RNA continues for more than 1 hr and presumptive histone messenger RNA is synthesized and transported into the cytoplasm where it is apparently associated with polyribosomes. Possible explanations of this result and its implications for the "informasome" theory of messenger transport in embryonic cells are discussed.

Synthesis and storage of microtubule proteins by sea urchin embryos.

Studies employing colchicine binding, precipitation with vinblastine sulfate, and acrylamide gel electrophoresis confirm earlier proposals that Arbacia punctulata and Lytechinus pictus eggs and embryos contain a store of microtubule proteins. Treatment of 150,000 g supernatants from sea urchin homogenates with vinblastine sulfate precipitates about 5% of the total soluble protein, and 75% of the colchicine-binding activity. Electrophoretic examination of the precipitate reveals two very prominent bands. These have migration rates identical to those of the A and B microtubule proteins of cilia. These proteins can be made radioactive at the 16 cell stage and at hatching by pulse labeling with tritiated amino acids. By labeling for 1 hr with leucine-(3)H in early cleavage, then culturing embryos in the presence of unlabeled leucine, removal of newly synthesized microtubule proteins from the soluble pool can be demonstrated. Incorporation of labeled amino acids into microtubule proteins is not affected by culturing embryos continuously in 20 microg/ml of actinomycin D. Microtubule proteins appear, therefore, to be synthesized on "maternal" messenger RNA. This provides the first protein encoded by stored or "masked" mRNA in sea urchin embryos to be identified.

Histone gene expression: progeny of isolated early blastomeres in culture make the same change as in the embryo.

Stage-specific changes in histone synthesis during sea urchin development reflect the expression of different sets of genes. The three kinds of blastomeres formed at the 16-cell stage are the earliest "determined" cells and fall into three distinct size classes. At this stage that cells synthesize only "early" histones. Such blastomeres can survive and divide in culture after being separated from the embryo, whether or not they are permitted to aggregate. With or without reaggregation, cultured progeny cells of each type of isolated blastomere perform the same changeover of histone synthesis as takes place in the intact embryo, that is, they begin spontaneously to synthesize a new set, the "late" histone variants. Normal contact relations among cells of the embryo are, therefore, not required for this programmed change in gene expression.

Continuity of protein synthesis through cleavage metaphase.

Protein synthesis continues without a decline in rate throughout the period of chromosome condensation and of cytokinesis in the first two cleavages of sea urchin embryos. The natural synchrony of the egg populations and the conditions of measurement allowed even a partial inhibition of synthesis to be observed. Our results do not explain the mechanism of inhibition of protein synthesis that occurs at metaphase in cultured mammalian cells, but it shows that such a change in rate is neither universal nor obligatory.

Sea urchin embryos are permeable to actinomycin.

When eggs and cleaving embryos of the sea urchin are exposed to [(3)H]actinomycin D, they become radioactive, and autoradiograms show that the radioactivity is inside the cells. At midcleavage, nuclei are more radioactive than cytoplasm. Extraction and chromatography of the intracellular labeled compounds identify them as actinomycin D and a water-soluable derivative. Conversion does not take place outside the cells. Treatment of embryos for 90 minutes with actinomycin D inhibits synthesis of RNA by more than 90 percent, leaving unaffected turnover of the pCpCpA terminals in transfer RNA. These data justify earlier interpretations of actinomycin experiments with embryos and justify use of the drug as a tool in the analysis of gene expression.

Thrombus stability explains the factor V Leiden paradox: a mouse model.

Humans carrying the factor V Leiden (FVL) variant have a fivefold increased risk for venous thrombosis. However, incidence of deep vein thrombosis (DVT) is proportionally greater than that of pulmonary embolism (PE) in these individuals. This is known as the FVL paradox. We hypothesized that the rate of initial DVT development is similar in FVL and noncarriers, but thrombi in FVL carriers are more stable and develop into a clinically significant DVT more often than in noncarriers. To test this, we induced thrombi in the femoral vein of wild-type (WT), heterozygous (F5L/+), and FVL homozygous (F5L/L) mice. Using intravital microscopy, thrombus size and embolization were visualized and emboli in the lungs were quantified. Compared with WT, femoral vein thrombi in F5L/+ and F5L/L mice were larger and embolized less. Total and large embolic events, the percentage of thrombus that embolized, and PE burden were significantly decreased in F5L/L mice. This suggests that in noncarriers (reflected by WT), a minor injury initially resulting in a small DVT tends to remain small and asymptomatic because of the embolization of the otherwise growing thrombus. Alternatively, the same insult in people with FVL (reflected by F5L/L) leads to thrombus growth as a result of less embolization, and thus symptomatic DVT development.

Application of spectral phase shaping to high resolution CARS spectroscopy.

By spectral phase shaping of both the pump and probe pulses in coherent anti-Stokes Raman scattering (CARS) spectroscopy we demonstrate the extraction of the frequencies, bandwidths and relative cross sections of vibrational lines. We employ a tunable broadband Ti:Sapphire laser synchronized to a ps-Nd:YVO mode locked laser. A high resolution spectral phase shaper allows for spectroscopy with a precision better than 1 cm(-1) in the high frequency region around 3000 cm(-1). We also demonstrate how new spectral phase shaping strategies can amplify the resonant features of isolated vibrations to such an extent that spectroscopy and microscopy can be done at high resolution, on the integrated spectral response without the need for a spectrograph.

Efficacy of cinacalcet administered with the first meal after dialysis: the SENSOR Study.

BACKGROUND: Cinacalcet, a novel calcimimetic, simultaneously lowers parathyroid hormone (PTH), phosphorus (P), calcium (Ca) and Ca x P in patients who are on dialysis with secondary hyperparathyroidism (sHPT) associated with CKD. Previous studies have required cinacalcet to be administered during the dialysis session and at the same time on non-dialysis days. The aim of the SENSOR study was to demonstrate that cinacalcet given in a more clinically practical manner with the first major meal after dialysis is noninferior to cinacalcet given with food during the dialysis session. METHODS: In this open-label study dialysis patients with poorly controlled sHPT (intact PTH (iPTH) (3) 300 pg/ml) were randomized to receive cinacalcet either daily with their post-dialysis meal (n = 337) or with food during the dialysis session (n = 336). The primary endpoint was the proportions of patients with mean iPTH pound 300 pg/ml ( pound 31.8 pmol/l) at Weeks 11 and 13 of a 21-week treatment period. Secondary endpoints included the proportion of patients with Ca x P < 55 mg2/dl2 (< 4.44 mmol2/l2) at Weeks 11 and 13 and patients who discontinued the study due to nausea or vomiting. RESULTS: Comparable proportions of patients in the cinacalcet "during dialysis" and "post-dialysis meal" groups had a mean iPTH pound 300 pg/ml (54 vs. 57%, respectively, 95% confidence interval (CI) difference -4, +10%) and Ca x P < 55 mg2/dl2 (78 vs. 73%, respectively, 95% CI difference -11, +2%) at Weeks 11 and 13. The groups were also comparable at Week 21. Cinacalcet was well tolerated, with < 3% of patients in both groups discontinuing due to nausea or vomiting. A combined post-hoc analysis of both groups showed the incidence of nausea and vomiting was lower if cinacalcet was administered during the evening. CONCLUSIONS: Administering cinacalcet with the first main meal after dialysis was as effective as administration with food during the dialysis session. Cinacalcet was well tolerated. The incidence of gastrointestinal adverse events appeared to be lower when cinacalcet was administered in the evening.

Low-level laboratory measurement of xenon radionuclides: Electron-photon versus photon measurements.

Radioactive xenon (mainly 131mXe, 133Xe, 133mXe and 135Xe) are tracked as markers of nuclear weapons testing. The CEA has developed the PIPSBox, a measurement cell able to detect electrons emitted by xenon nuclides. Combined with an ultra-low background γ spectrometer, electron detection capacities allow reaching minimum detectable activities (MDA) for a 3-day long measurement of about 0.5mBq for the four xenon radionuclides. Compared to a classical measurement cell, MDAs are improved by a factor of 2-4.

SPALAX NG: A breakthrough in radioxenon field measurement.

Lessons-learned from 10 years of noble gas stations operation and dedicated R&D allowed the design of a New Generation of station. In order to produce 60m3 air equivalent Xenon samples every 8h, it implements: (i) larger sampler unit for Xenon extraction (2 compressors and 8 nitrogen membranes), (ii) new noble gas adsorbent (Ag@ZSM5), (iii) hardened components and (iv) new high resolution coincidence low background spectrometer (HPGe/PIPSBox). Station expected radioxenon sensitivity is lower than 0.3mBq/m3.

A precise method to determine the angular distribution of backscattered light to high angles.

We present an approach to measure the angular dependence of the diffusely scattered intensity of a multiple scattering sample in backscattering geometry. Increasing scattering strength give rise to an increased width of the coherent backscattering and sets higher demands on the angular detection range. This is of particular interest in the search for the transition to Anderson localization of light. To cover a range of -60 degrees to +85 degrees from direct back-reflection, we introduced a new parallel intensity recording technique. This allows one-shot measurements, with fast alignment and short measuring time, which prevents the influence of illumination variations. Configurational average is achieved by rotating the sample and singly scattered light is suppressed with the use of circularly polarized light up to 97%. This implies that backscattering enhancements of almost two can be achieved. In combination with a standard setup for measuring small angles up to +/-3 degrees , a full characterization of the coherent backscattering cone can be achieved. With this setup we are able to accurately determine transport mean free paths as low as 235 nm.

Ground surface ultralow background spectrometer: Active shielding improvements and coincidence measurements for the Gamma3 spectrometer.

The ultralow background versatile spectrometer GAMMA3 has been optimized with the following shielding improvements: (i) optimized nitrogen injection flux of 300Lh-1, and (ii) cosmic veto configuration with 9 scintillating plates. These improvements allow a reduction of 39% of the normalized integral background count rate down to 2.7±0.2min-1kgGe-1 (40-2500keV energy range). Minimum Detectable Activities when performing direct γ-ray spectrometry or γ-γ coincidence spectrometry are compared.