To stop or not to stop novel oral anticoagulants prior to performing joint interventional maneuvers? Evidence from a prospective study that the therapy can be maintained.

Anticoagulation is common in patients undergoing routine musculoskeletal interventional maneuvers. Previous retrospective studies have established the safety of continuing anticoagulation with novel oral anticoagulants (NOACs) when performing this kind of interventions. Indeed, ultrasound (US)-guided interventional maneuvers have shown a superior safety profile compared to blind anatomical maneuvers. To evaluate prospectively the periprocedural bleeding events in NOAC-anticoagulated patients undergoing interventional articular or periarticular procedures. Consecutive patients diagnosed with inflammatory or degenerative rheumatologic pathology requiring interventional maneuvers were prospectively recruited. Group 1 was treated with NOACs, group 2 was treated with vitamin K antagonists, and group 3 was not anticoagulated. Prior to the international maneuver, NOAC therapy was continuously administered, in regimens dictated by the underlying anticoagulation indication. Demographics, comorbidities, laboratory parameters, locally administered medication (corticosteroids or viscosupplementation), interventional maneuver location, needle size, and local bleeding events were recorded. Post-procedural control was performed at 30 min, 48 h, and 7 days. No articular/periarticular bleeding event occurred in patients treated with NOACs, regardless of their type and dosage, locally administered medication, needle size, location, and number of interventions per individual. Several patients in all groups developed small superficial ecchymoses at the injection site. Our results suggest that NOACs are safe to be used in a continuous regimen prior to US-guided injections, even as dual antithrombotic therapy (in combination with aspirin). The use of lower gauge needles, chosen for viscosupplementation therapy, was not burdened with adverse effects on the procedural outcome. Key Points • Currently, no prospective studies have been performed to establish the safety of continuous NOAC anticoagulation when performing routine intra- or periarticular interventional maneuvers. • The study offers an extensive view on a wide spectrum of intra- and periarticular interventional maneuvers including anatomic targets and needle sizes that were not previously assessed. • The study offers a perspective into performing repetitive maneuvers in the same patient, both over a short time and at longer intervals. • The zero periprocedural bleeding risk observed in our study may reassure practitioners and suggest that US-guided interventional therapeutic interventions are safe in patients treated with a continuous regimen of different NOACs.

Nonlinear optical responses in two-dimensional transition metal dichalcogenide multilayer: WS2, WSe2, MoS2 and Mo0.5W0.5S2: publisher's note.

This publisher's note amends the Funding section of a recent publication [Opt. Express24, 20685 (2016].

Nonlinear optical responses in two-dimensional transition metal dichalcogenide multilayer: WS2, WSe2, MoS2 and Mo 0.5 W0.5 S2.

Synthetic two-dimensional transition metal dichalcogenides such as, tungsten disulphide (WS2), tungsten diselenide (WSe2), molybdenum disulphide (MoS2) as well as mixed molybdenum tungsten disulphide (Mo0.5W0.5S2) single crystals were grown by the chemical vapor transport method using halogens (bromine or chlorine) as transport agents. Multi- layer samples were cleaved from the single crystals, and their nonlinear optical (NLO) properties were obtained from both open aperture and closed aperture Z-scan measurements using a picosecond mode-locked Nd: YAG laser operating at a wavelength of 1064 nm, with pulse duration of 25 ps, and 20 Hz repetition rate. Both WS2 and MoS2 exhibited nonlinear saturable absorption (SA), whereas WSe2 and Mo0.5W0.5S2 showed nonlinear two-photon absorption (2PA). A large 2PA coefficient ß as high as + 1.91x10-8 cm/W was obtained for the Mo0.5W0.5S2, and an index of refraction coefficient γ = -2.47x10-9 cm2/W was obtained for the WSe2 sample.

Low doses of nicotine and ethanol induce CYP2E1 and chlorzoxazone metabolism in rat liver.

The use of ethanol and nicotine is strongly linked; 80 to 95% of heavy alcohol users are also smokers. In humans, cigarette smoking significantly enhances CYP2E1 activity, as measured by increased metabolism of chlorzoxazone in vivo. CYP2E1 metabolizes ethanol and can generate toxic intermediates. CYP2E1 also bioactivates tobacco smoke and other procarcinogens and several hepatotoxins. We hypothesized that, like ethanol, nicotine increases CYP2E1 activity. Rats were treated once daily with saline, ethanol (0.3, 1.0, and 3.0 g/kg p.o.), or nicotine bitartrate (0.1, 0.3, and 1.0 mg base/kg s.c.) for 7 days. After ethanol or nicotine administration, immunostaining for CYP2E1 was increased in the centrilobular regions of rat liver. Western blot analyses revealed that hepatic CYP2E1 levels were increased by ethanol (1.6-2.4-fold) and nicotine (1.3-1.7-fold). In vitro chlorzoxazone 6-hydroxylation analyses demonstrated elevated Vmax values (compared with saline-treated animals) by using hepatic microsomes from high-dose ethanol (2.27 +/- 0.12 versus 1.18 +/- 0.23 nmol/mg/min, p < 0.001) or nicotine-treated rats (2.35 +/- 0.04 versus 1.32 +/- 0.55 nmol/mg/min, p < 0.005), with no change in affinity. The magnitude of enhanced chlorzoxazone metabolism by microsomes from drug-treated animals is consistent with the observed increase in CYP2E1 protein by immunoblot. These data suggest that nicotine may increase CYP2E1-induced toxicity and contribute to cross-tolerance in smokers and people treated with nicotine (e.g., smokers, patients with Alzheimer's disease, ulcerative colitis, neuropsychiatric motor disorders).

Correlated intramolecular motions and diffuse X-ray scattering in lysozyme.

Correlated motions of protein atoms are of biological significance in processes involving ligand binding, conformational change and information transmission. X-ray scattering patterns from protein crystals contain diffuse scattering that originates from correlated displacements of atoms. Here we present experimental data on diffuse X-ray scattering from lysozyme crystals. We show that the diffuse scattering is similar in form to scattering derived from molecular dynamics simulation and normal mode analysis of the isolated protein, the normal modes giving the closest agreement with experiment.