Near-UV photodissociation dynamics of CH2I2

The near-UV photodissociation dynamics of CH2I2 has been investigated using a combination of velocitymap (slice) ion imaging and ab initio calculations characterizing the excited states. Ground state I(2 P3/2) and spin-orbit excited I*(2 P1/2) atoms were probed using 2+1 resonance-enhanced multiphoton ionization (REMPI) or with single-photon VUV ionization. Two-color ion images were recorded at pump wavelengths of 355 nm, 266 nm and 248 nm, and one-color ion images at the REMPI wavelengths of ~304 nm and ~280 nm. Analysis of the ion images shows that, regardless of iodine spin-orbit state, ~20% of the available energy is partitioned into translation ET at all excitation wavelengths indicating that the CH2I co-fragment is formed highly internally excited. The translational energy distributions comprise a slow, “statistical” component that peaks near zero and faster components that peak away from zero. The slow component makes an increasingly large contribution to the distribution as the excitation wavelength is decreased. The C–I bond dissociation energy of D0 = 2.155±0.008 eV is obtained from the trend in the ET release of the faster components with increasing excitation energy. The I and I* ion images are anisotropic, indicating prompt dissociation, and are characterized by β parameters that become increasingly positive with increasing ET. The decrease in β at lower translational energies can be attributed to deviation from axial recoil. MRCI calculations including spin-orbit coupling have been performed to identify the overlapping features in the absorption spectrum and characterize onedimensional cuts through the electronically excited potential energy surfaces. The excited states are of significantly mixed singlet and triplet character. At longer wavelengths, excitation directly accesses repulsive states primarily of B1 symmetry, consistent with the observed !β∀, while shorter wavelengths accesses bound states, also of B1 symmetry that are crossed by repulsive states

Colloidal Gold - A Powerful Tool in Scanning Electron Microscope Immunocytochemistry: An Overview of Bioapplications

Colloidal gold may be conjugated to a wide variety of macromolecules, provides a versatile system for immunocytochemical studies by various types of microscopy (light and fluorescent microscopy, scanning (SEM) and transmission (TEM) electron microscopy), and is significantly contributing to the development of SEM immunocytochemistry as a routine analytical procedure. A comprehensive overview has been compiled of the literature on SEM bioapplications of colloidal gold. This is illustrated through a selected series of studies focussing on a) cell surface receptor-ligand interactions; b) expression of cell surface lectin-binding sites; c) surface distribution of extracellular matrix components; and d) visualization of gold-labelled cytoskeletal elements with emphasis on the use of backscattered electron imaging as a powerful analytical adjunct in the development of SEM immunocytochemistry

Plasma oxalate: comparison of methodologies

Measurement of oxalate in the blood is essential for monitoring primary hyperoxaluria patients with progressive renal impairment and on dialysis prior to transplantation. As no external quality assurance scheme is available for this analyte, we conducted a sample exchange scheme between six laboratories specifcally involved with the investigation of primary hyperoxaluria to compare results. The methodologies compared were gas chromatography/mass spectrometry (GCMS), ion chromatography with mass spectrometry (ICMS), and enzymatic methods using oxalate oxidase and spectrophotometry. Although individual laboratories performed well in terms of reproducibility and linearity, there was poor agreement (absolute values) between centres as illustrated by a longer-term comparison of patient results from two of the participating laboratories. This situation was only partly related to diferences in calibration and mainly refected the lower recoveries seen with the ultrafltration of samples. These fndings lead us to conclude that longitudinal monitoring of primary hyperoxaluria patients with deteriorating kidney function should be performed by a single consistent laboratory and the methodology used should always be defned. In addition, plasma oxalate concentrations reported in registry studies and those associated with the risk of systemic oxalosis in published studies need to be interpreted in light of the methodology used. A reference method and external quality assurance scheme for plasma oxalate analysis would be benefcial

Combining Science with Art to Educate and Motivate Patients Prior to Colorectal Cancer Screening

Colorectal cancer (CRC) is the second leading cause of cancer deaths in the US despite wide use of colonoscopy to prevent CRC and CRC-related mortality. Colonoscopy is used to identify and remove lesions that will lead to cancer, however, most deaths occur because lesions are not detected or completely removed during the procedure. Patients play a crucial role in the detection component of colonoscopy: the better the colon is prepared, the higher the chance of detection of all polyps and cancers. In general, patients are instructed to clean the colon by way of a paper or web-based form that lists the objective (scientific) steps involved; unfortunately this too often does not result in a well-prepared colon. Behavior is known to be heavily influenced by emotion. As the first phase of a smart education research project we created an artistic and instructional documentary in which patients engage with the educational content through emotional responses; i.e., we motivate patients to follow instructions by combining scientific with emotional aspects of CRC prevention including preparation of the colon prior to colonoscopy. In the second research phase we will test whether use of the documentary results in improved colon preparation

UV Photodissociation Dynamics of CHI2Cl and its Role as a Photolytic Precursor for a Chlorinated Criegee Intermediate

Photolysis of geminal diiodoalkanes in the presence of molecular oxygen has become an established route to the laboratory production of several Criegee intermediates, and such compounds also have marine sources. Here, we explore the role that the trihaloalkane, chlorodiiodomethane (CHI2Cl), may play as a photolytic precursor for the chlorinated Criegee intermediate ClCHOO. CHI2Cl has been synthesized and its UV absorption spectrum measured; relative to that of CH2I2 the spectrum is shifted to longer wavelength and the photolysis lifetime is calculated to be less than two minutes. The photodissociation dynamics have been investigated using DC slice imaging, probing ground state I and spin-orbit excited I* atoms with 2+1 REMPI and single-photon VUV ionization. Total translational energy distributions are bimodal for I atoms and unimodal for I*, with around 72% of the available energy partitioned in to the internal degrees of freedom of the CHICl radical product, independent of photolysis wavelength. A bond dissociation energy of D0 = 1.73±0.11 eV is inferred from the wavelength dependence of the translational energy release, which is slightly weaker than typical C–I bonds. Analysis of the photofragment angular distributions indicate dissociation is prompt and occurs primarily via transitions to states of A″ symmetry. Complementary high-level MRCI calculations, including spin-orbit coupling, have been performed to characterize the excited states and confirm that states of A″ symmetry with highly mixed singlet and triplet character are predominantly responsible for the absorption spectrum. Transient absorption spectroscopy has been used to measure the absorption spectrum of ClCHOO produced from the reaction of CHICl with O2 over the range 345–440 nm. The absorption spectrum, tentatively assigned to the syn conformer, is at shorter wavelengths relative to that of CH2OO and shows far weaker vibrational structure

Immunological predictors of CD4+ T cell decline in antiretroviral treatment interruptions

<p>Abstract</p> <p>Background</p> <p>The common response to stopping anti-HIV treatment is an increase of HIV-RNA load and decrease in CD4⁺, but not all the patients have similar responses to this therapeutic strategy. The aim was to identify predictive markers of CD4⁺cell count declines to < 350/μL in CD4-guided antiretroviral treatment interruptions.</p> <p>Methods</p> <p>27 HIV-infected patients participated in a prospective multicenter study in with a 24 month follow-up. Patients on stable highly active antiretroviral therapy (HAART), with CD4⁺count > 600/μL, and HIV-RNA < 50 copies/ml for at least 6 months were offered the option to discontinue antiretroviral therapy. The main outcome was a decline in CD4⁺cell count to < 350/μL.</p> <p>Results</p> <p>After 24 months of follow-up, 16 of 27 (59%) patients (who discontinued therapy) experienced declines in CD4⁺cell count to < 350/μL. Patients with a CD4⁺nadir of < 200 cells/μL had a greater risk of restarting therapy during the follow-up (RR (CI95%): 3.37 (1.07; 10.36)). Interestingly, lymphoproliferative responses to <it>Mycobacterium tuberculosis </it>purified protein derivative (PPD) below 10000 c.p.m. at baseline (4.77 (1.07; 21.12)), IL-4 production above 100 pg/mL at baseline (5.95 (1.76; 20.07)) in PBMC cultured with PPD, and increased IL-4 production of PBMC with p24 antigen at baseline (1.25 (1.01; 1.55)) were associated to declines in CD4⁺cell count to < 350/μL.</p> <p>Conclusion</p> <p>Both the number (CD4⁺nadir) and the functional activity of CD4⁺(lymphoproliferative response to PPD) predict the CD4⁺decrease associated with discontinuation of ART in patients with controlled viremia.</p

A Mouse Model of Post-Arthroplasty Staphylococcus aureus Joint Infection to Evaluate In Vivo the Efficacy of Antimicrobial Implant Coatings

Post-arthroplasty infections represent a devastating complication of total joint replacement surgery, resulting in multiple reoperations, prolonged antibiotic use, extended disability and worse clinical outcomes. As the number of arthroplasties in the U.S. will exceed 3.8 million surgeries per year by 2030, the number of post-arthroplasty infections is projected to increase to over 266,000 infections annually. The treatment of these infections will exhaust healthcare resources and dramatically increase medical costs.To evaluate novel preventative therapeutic strategies against post-arthroplasty infections, a mouse model was developed in which a bioluminescent Staphylococcus aureus strain was inoculated into a knee joint containing an orthopaedic implant and advanced in vivo imaging was used to measure the bacterial burden in real-time. Mice inoculated with 5x10(3) and 5x10(4) CFUs developed increased bacterial counts with marked swelling of the affected leg, consistent with an acute joint infection. In contrast, mice inoculated with 5x10(2) CFUs developed a low-grade infection, resembling a more chronic infection. Ex vivo bacterial counts highly correlated with in vivo bioluminescence signals and EGFP-neutrophil fluorescence of LysEGFP mice was used to measure the infection-induced inflammation. Furthermore, biofilm formation on the implants was visualized at 7 and 14 postoperative days by variable-pressure scanning electron microscopy (VP-SEM). Using this model, a minocycline/rifampin-impregnated bioresorbable polymer implant coating was effective in reducing the infection, decreasing inflammation and preventing biofilm formation.Taken together, this mouse model may represent an alternative pre-clinical screening tool to evaluate novel in vivo therapeutic strategies before studies in larger animals and in human subjects. Furthermore, the antibiotic-polymer implant coating evaluated in this study was clinically effective, suggesting the potential for this strategy as a therapeutic intervention to combat post-arthroplasty infections

Frequency of the C9orf72 hexanucleotide repeat expansion in patients with amyotrophic lateral sclerosis and frontotemporal dementia: a cross-sectional study.

We aimed to accurately estimate the frequency of a hexanucleotide repeat expansion in C9orf72 that has been associated with a large proportion of cases of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)