Mechanism of Hydrogen-Bonded Complex Formation between Ibuprofen and Nanocrystalline Hydroxyapatite.

Nanocrystalline hydroxyapatite (nanoHA) is the main hard component of bone and has the potential to be used to promote osseointegration of implants and to treat bone defects. Here, using active pharmaceutical ingredients (APIs) such as ibuprofen, we report on the prospects of combining nanoHA with biologically active compounds to improve the clinical performance of these treatments. In this study, we designed and investigated the possibility of API attachment to the surface of nanoHA crystals via the formation of a hydrogen-bonded complex. The mechanistic studies of an ibuprofen/nanoHA complex formation have been performed using a holistic approach encompassing spectroscopic (Fourier transform infrared (FTIR) and Raman) and X-ray diffraction techniques, as well as quantum chemistry calculations, while comparing the behavior of the ibuprofen/nanoHA complex with that of a physical mixture of the two components. Whereas ibuprofen exists in dimeric form both in solid and liquid state, our study showed that the formation of the ibuprofen/nanoHA complex most likely occurs via the dissociation of the ibuprofen dimer into monomeric species promoted by ethanol, with subsequent attachment of a monomer to the HA surface. An adsorption mode for this process is proposed; this includes hydrogen bonding of the hydroxyl group of ibuprofen to the hydroxyl group of the apatite, together with the interaction of the ibuprofen carbonyl group to an HA Ca center. Overall, this mechanistic study provides new insights into the molecular interactions between APIs and the surfaces of bioactive inorganic solids and sheds light on the relationship between the noncovalent bonding and drug release properties

Search for the standard model Higgs boson in the H to ZZ to 2l 2nu channel in pp collisions at sqrt(s) = 7 TeV

A search for the standard model Higgs boson in the H to ZZ to 2l 2nu decay channel, where l = e or mu, in pp collisions at a center-of-mass energy of 7 TeV is presented. The data were collected at the LHC, with the CMS detector, and correspond to an integrated luminosity of 4.6 inverse femtobarns. No significant excess is observed above the background expectation, and upper limits are set on the Higgs boson production cross section. The presence of the standard model Higgs boson with a mass in the 270-440 GeV range is excluded at 95% confidence level.Comment: Submitted to JHE

Combined search for the quarks of a sequential fourth generation

Results are presented from a search for a fourth generation of quarks produced singly or in pairs in a data set corresponding to an integrated luminosity of 5 inverse femtobarns recorded by the CMS experiment at the LHC in 2011. A novel strategy has been developed for a combined search for quarks of the up and down type in decay channels with at least one isolated muon or electron. Limits on the mass of the fourth-generation quarks and the relevant Cabibbo-Kobayashi-Maskawa matrix elements are derived in the context of a simple extension of the standard model with a sequential fourth generation of fermions. The existence of mass-degenerate fourth-generation quarks with masses below 685 GeV is excluded at 95% confidence level for minimal off-diagonal mixing between the third- and the fourth-generation quarks. With a mass difference of 25 GeV between the quark masses, the obtained limit on the masses of the fourth-generation quarks shifts by about +/- 20 GeV. These results significantly reduce the allowed parameter space for a fourth generation of fermions.Comment: Replaced with published version. Added journal reference and DO

Minimally Invasive Video-Assisted Parathyroidectomy: Lesson Learned from 137 cases

Abstract: Background: Since February 1997, a technique of minimally invasive video-assisted parathyroidectomy (MIVAP) was developed at our institution for the treatment of sporadic primary hyperparathyroidism (sPHPT). In this study we analyzed the entire series of patients who underwent MIVAP during the last 3 years. Study Design: One hundred thirty-seven patients with sPHPT were selected for MIVAP. Selection criteria were: diagnosis of single adenoma based on preoperative localization studies (ultrasonography, sestamibi scintigraphy, or both), and no previous neck surgery or concomitant large multinodular goiter. The procedure, already described, is performed by a gasless video-assisted technique through a single 1.5-cm central skin incision above the sternal notch. Quick, intraoperative parathyroid hormone assay was used in 134 cases (97.8%) to confirm the complete removal of all hyperfunctioning parathyroid tissue. Results: Mean operative time was 54.3 +/- 22.6 minutes. The conversion rate was 8.8%. One laryngeal nerve palsy was registered (0.7%), as was one case of persistent hyperparathyroidism. In six patients (4.4%) a transient symptomatic postoperative hypocalcemia was observed. Two thyroid lobectomies were associated using the same minimally invasive access. At a mean followup of 15.4 +/- 10.6 months, all but two patients were normocalcemic. The cosmetic result was considered excellent by most of the patients (92.8%). Conclusions: Although not all patients with sPHPT are eligible for MIVAP, this approach can now be proposed in a bigger proportion (67% of patients). As already demonstrated in a previous study, also in a large series of patients, after greater experience has been achieved, the results and the operative time are the same as in traditional surgery, with better cosmetic result and a less painful course. (J Am Coll Surg 2000; 191:613-618. (C) 2000 by the American College of Surgeons)